Publications


The association of metformin use with prostate cancer aggressiveness among Black Americans and White Americans in a population-based study.
Publication Type:
Article
Year of Publication:
2018
Author(s):
Khan S, Cai J, Nielsen ME, Troester MA, Mohler JL, Fontham ETH, Farnan L, Drake BF, Olshan AF, Bensen JT.
Source:
Cancer Causes and Control
Volume:
29
Issue:
11
Publication Date:
November 2018
Pagination:
1143-50

Abstract

PURPOSE: Metformin has been associated with a reduced incidence of prostate cancer and improved prostate cancer outcomes. However, whether race modifies the association between metformin use and prostate cancer aggressiveness remains uncertain. The association between metformin use and prostate cancer aggressiveness was examined separately in Black Americans (Blacks) and White Americans (Whites).

METHODS: The study population consisted of 305 Black and 195 White research participants with incident prostate cancer and self-reported diabetes from the North Carolina-Louisiana Prostate Cancer Project. High-aggressive prostate cancer was defined using a composite measure of Gleason sum, prostate-specific antigen, and clinical stage. Multivariable logistic regression was used to assess the association between metformin use and high-aggressive prostate cancer at diagnosis, separately among Whites and Blacks, with adjustment for age, screening history, site, education, insurance, and body mass index.

RESULTS: Metformin use was associated positively with high-aggressive prostate cancer in Blacks (OR 2.01; 95% CI 1.05, 3.83). By contrast, a weak inverse association between metformin use and high-aggressive prostate cancer was found in Whites (OR 0.80, 95% CI 0.34, 1.85).

CONCLUSIONS: The association between metformin use and prostate cancer aggressiveness may be modified by race.

KEYWORDS: Aggressiveness; Black Americans; Metformin; PCaP; Prostate cancer
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Dietary patterns based on the Mediterranean diet and DASH diet are inversely associated with high aggressive prostate cancer in PCaP.
Publication Type:
Article
Year of Publication:
2019
Author(s):
Schneider L, Su LJ, Arab L, Bensen JT, Farnan L, Fontham ETH, Song L, Hussey J, Merchant AT, Mohler JL, Steck SE.
Source:
Annals of Epidemiology
Volume:
29
Issue:
e1
Publication Date:
January 2019
Pagination:
16-22

Abstract

Background: Several foods and nutrients have been linked to the development of prostate cancer, but the association between healthy dietary patterns and prostate cancer aggressiveness is less studied. The aim of this study was to evaluate the relationship between the Mediterranean diet (MED) and Dietary Approaches to Stop Hypertension (DASH) diet scores and prostate cancer aggressiveness by race.

Methods: Data from the population-based, case-only North Carolina-Louisiana Prostate Cancer Project (PCaP) were used to examine the association between diet quality, measured by MED and DASH scores, and prostate cancer aggressiveness in 1899 African American (AA) and European American (EA) research subjects. Dietary intake was assessed using a modified National Cancer Institute Diet History Questionnaire. Logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for high versus low-intermediate aggressive prostate cancer.

Results: Higher MED scores were inversely associated with high aggressive prostate cancer overall (OR: 0.66; 95% CI: 0.46, 0.95 for high versus low scores); results were similar for AA and EA men. A weaker inverse association between DASH scores and prostate cancer aggressiveness was found (OR: 0.76; 95% CI: 0.55, 1.06).

Conclusions: Higher diet quality, as represented by a Mediterranean-style diet or DASH diet, may reduce the odds of high aggressive prostate cancer.
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Statin use, high cholesterol and prostate cancer progression; results from HCaP-NC.
Publication Type:
Article
Year of Publication:
2018
Author(s):
Allott EH, Farnan L, Steck SE, Song L, Arab L, Su LJ, Fontham ETH, Mohler JL, Bensen JT.
Source:
The Prostate
Volume:
78
Issue:
11
Publication Date:
August 2018
Pagination:
857-864

Abstract

BACKGROUND: Statin use is associated with lower advanced prostate cancer risk and reduced prostate cancer-specific mortality, but prior studies were conducted mainly in white men. We examined the effect of statin use on risk of prostate cancer progression in a population-based, minority-enriched cohort.

METHODS: We used data from prostate cancer cases (45% African American) diagnosed between 2004 and 2007 who participated in the Health Care Access and Prostate Cancer Treatment in North Carolina cohort (HCaP-NC). We abstracted statin use at diagnosis. Men reported if they had ever been diagnosed with high cholesterol. Multivariable Cox proportional hazards analysis was used to examine associations between statin use and risk of prostate cancer progression (biochemical recurrence or secondary treatment), overall and by race. In secondary analysis, we examined the association between high cholesterol and risk of progression, overall, and by statin use.

RESULTS: Of 669 men, 244 (36%) were statin users at diagnosis. During 3.8 years median follow-up, 138 men experienced prostate cancer progression. There was no association between statin use and risk of progression, either overall (HR 1.03; 95%CI 0.72-1.46) or stratified by race. High cholesterol was inversely associated with risk of progression, particularly among statin users (HR 0.43; 95%CI 0.20-0.94; p-interaction = 0.22) and in men with higher perceived access to care (HR 0.57; 95%CI 0.36-0.90; p-interaction = 0.03). Study limitations included a relatively small sample size, short follow-up, and lack of data regarding post diagnosis statin use.

CONCLUSIONS: Statin use at diagnosis was not associated with prostate cancer progression in the population-based, minority-enriched HCaP-NC. Greater healthcare engagement, including actively controlling serum cholesterol, may be linked to better prostate cancer-specific outcomes.

KEYWORDS: access to care; health literacy; high cholesterol; prostate cancer progression; race; radiation; radical prostatectomy; statin
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Modelling attrition and nonparticipation in a longitudinal study of prostate cancer.
Publication Type:
Article
Year of Publication:
2018
Author(s):
Spiers S, Oral E, Fontham ETH, Peters ES, Mohler JL, Bensen JT, Brennan CS.
Source:
BMC Medical Research Methodology
Volume:
18
Issue:
1
Publication Date:
June 2018
Pagination:
60

Abstract

Background: Attrition occurs when a participant fails to respond to one or more study waves. The accumulation of
attrition over several waves can lower the sample size and power and create a final sample that could differ in
characteristics than those who drop out. The main reason to conduct a longitudinal study is to analyze repeated
measures; research subjects who drop out cannot be replaced easily. Our group recently investigated factors
affecting nonparticipation (refusal) in the first wave of a population-based study of prostate cancer. In this study we
assess factors affecting attrition in the second wave of the same study. We compare factors affecting
nonparticipation in the second wave to the ones affecting nonparticipation in the first wave.

Methods: Information available on participants in the first wave was used to model attrition. Different sources of
attrition were investigated separately. The overall and race-stratified factors affecting attrition were assessed. Kaplan-
Meier survival curve estimates were calculated to assess the impact of follow-up time on participation.

Results: High cancer aggressiveness was the main predictor of attrition due to death or frailty. Higher Charlson
Comorbidity Index increased the odds of attrition due to death or frailty only in African Americans (AAs). Young
age at diagnosis for AAs and low income for European Americans (EAs) were predictors for attrition due to lost to
follow-up. High cancer aggressiveness for AAs, low income for EAs, and lower patient provider communication
scores for EAs were predictors for attrition due to refusal. These predictors of nonparticipation were not the same
as those in wave 1. For short follow-up time, the participation probability of EAs was higher than that of AAs.

Conclusions: Predictors of attrition can vary depending on the attrition source. Examining overall attrition
(combining all sources of attrition under one category) instead of distinguishing among its different sources should
be avoided. The factors affecting attrition in one wave can be different in a later wave and should be studied
separately.

Keywords: Unit nonresponse, Nonresponse bias, Attrition, Longitudinal study, Prostate cancer
Show Abstract

Calcium, magnesium, and whole-milk intakes and high-aggressive prostate cancer in the North Carolina-Louisiana Prostate Cancer Project (PCaP).
Publication Type:
Article
Year of Publication:
2018
Author(s):
Steck SE, Omofuma OO, Su LJ, Maise AA, Woloszynska-Read A, Johnson CS, Zhang H, Bensen JT, Fontham ETH, Mohler JL, Arab L.
Source:
American Journal of Clinical Nutrition
Volume:
1
Issue:
107
Publication Date:
May 2018
Pagination:
799-807

Abstract

Background: Calcium and dairy product intakes have been positively associated with prostate cancer risk. An imbalance in concentrations of calcium and magnesium has been associated with multiple chronic diseases, although few studies have examined the relation with prostate cancer aggressiveness.

Objective: The goal of this study was to examine the association between dietary intakes of calcium and magnesium, the calcium-to-magnesium ratio (Ca:Mg), and dairy products and prostate cancer aggressiveness.

Design: Dietary intake was assessed with the use of an interviewer-administered modified National Cancer Institute Diet History Questionnaire in 996 African American and 1064 European American men with a recent histologically confirmed diagnosis of prostate cancer from the North Carolina-Louisiana Prostate Cancer Project (PCaP). High-aggressive disease was defined as Gleason sum ≥8, or prostate-specific antigen (PSA) >20 ng/mL, or Gleason score ≥7 and clinical stage T3-T4. The comparison group was all other prostate cancer cases. Logistic regression was used to determine the adjusted ORs and 95% CIs for high-aggressive prostate cancer by tertile of diet and supplement exposures.

Results: There was a positive association across tertiles of dietary Ca:Mg intake, with odds of high-aggressive prostate cancer in the upper tertiles as follows-OR for tertile 2 compared with tertile 1: 1.38 (95% CI: 1.01, 1.88); OR for tertile 3 compared with tertile 1: 1.46 (95% CI: 1.06, 2.02). When stratified by race, the positive association was more pronounced in African American men (OR for tertile 3 compared with tertile 2: 1.62; 95% CI: 1.04, 2.53). Men who reported the highest daily consumption of whole-fat milk had a 74% increased odds of high-aggressive prostate cancer compared with non-whole-fat milk drinkers, which was attenuated after adjustment for potential mediating factors, such as saturated fat and Ca:Mg intake.

Conclusions: Among both African American and European American men diagnosed with prostate cancer, a higher Ca:Mg and whole-milk intake were associated with higher odds of high-aggressive prostate cancer. This study was registered at www.clinicaltrials.gov as NCT03289130.
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Association among plasma 1,25(OH)2D and ratio of 25(OH)D to 1,25(OH)2D with prostate cancer aggressiveness.
Publication Type:
Article
Year of Publication:
2019
Author(s):
Steck SE, Woloszynska-Read A, Rmaskrishnan S, Arab L, Zhang H, Bensen JT, Fontham ETH, Johnson CS, Mohler JL, Smith GJ, Su LJ.
Source:
The Prostate
Volume:

Issue:

Publication Date:
May 2019
Pagination:

Abstract

BACKGROUND: African-American (AA) men tend to present with more aggressive prostate cancer (Gleason score >7) than European-American (EA) men. Vitamin D and its metabolites are implicated in prostate cancer biology with vitamin D deficiency, indicated by its metabolite levels in serum or plasma, usually observed in AA men.

OBJECTIVE: To determine if 1, 25-dihydroxy vitamin D3 [1,25(OH)2 D] plasma levels in AA and EA prostate cancer patients alter the risk of having aggressive prostate cancer.

DESIGN: Research subjects from the North Carolina-Louisiana Prostate Cancer Project (AA n = 435 and EA n = 532) were included. Plasma metabolites 1,25(OH)2 D and 25-hydroxyvitamin D3 [25(OH)D] were measured using liquid chromatography with tandem mass spectrophotometry. Research subjects were classified into low (Gleason sum < 7, stage T1-T2, and Prostate-specific antigen (PSA) < 9 ng/mL) or high (Gleason sum > 8 or Gleason sum = 7 with 4 + 3, or PSA > 20 ng/mL, or Gleason sum = 7 and stage T3-T4) aggressive disease.

RESULTS: Research subjects in the second and third tertiles of plasma levels of 1, 25(OH)2 D had lower odds of high aggressive prostate cancer (AA [ORT2vsT1 : 0.66, 95%CI: 0.39-1.12; ORT3vsT1 : 0.83, 95%CI: 0.49-1.41] and EA [ORT2vsT1 : 0.68, 95%CI: 0.41-1.11; ORT3vsT1 : 0.67, 95%CI: 0.40-1.11]) compared with the first tertile, though confidence intervals included the null. Greater 1,25(OH)2 D/25(OH)D molar ratios were associated with lower odds of high aggressive prostate cancer more evidently in AA (ORQ4vsQ1 : 0.45, CI: 0.24-0.82) than in EA (ORQ4vsQ1 : 0.64, CI: 0.35-1.17) research subjects.

CONCLUSIONS: The 1,25(OH)2 D/25(OH)D molar ratio was associated with decreased risk of high aggressive prostate cancer in AA men, and possibly in EA men. Further studies analyzing vitamin D polymorphisms, vitamin D binding protein levels, and prostatic levels of these metabolites may be useful. These studies may provide a better understanding of the vitamin D pathway and its biological role underlying health disparities in prostate cancer.
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Adherence to World Cancer Research Fund/American Institute for Cancer Research lifestyle recommendations reduces prostate cancer aggressiveness among African and Caucasian Americans.
Publication Type:
Article
Year of Publication:
2013
Author(s):
Arab L, Su J, Steck SE, Ang A, Fontham ET, Bensen JT, Mohler JL.
Source:
Nutr Cancer
Volume:
65
Issue:
5
Publication Date:
2013
Pagination:
633-43

Abstract

The effect of adherence to the World Cancer Research Fund (WCRF) lifestyle recommendations on cancer aggressiveness is unknown. We examined associations between adherence to recommendations and risk of highly aggressive prostate cancer in research subjects enrolled in the North Carolina-Louisiana Prostate Cancer Project (PCaP). We examined associations between adherence to WCRF recommendations and risk of highly aggressive prostate cancer among 2212 newly diagnosed African Americans (AA) or Caucasian Americans (CA) aged 40-70 years in PCaP. Prostate cancer aggressiveness was based on Gleason scores, serum prostate-specific antigens, and TNM stage. Adherence to WCRF recommendations was based on point scores and odds ratios estimated. Results showed that adherence to recommendations was significantly and negatively associated with risk of a highly aggressive prostate cancer. Each additional point in the total adherence score corresponded to a 13% risk reduction. Total adherence score <4 predicted increased risk in both AA (OR = 1.36; 95% CI = 1.01-1.85) and CA (OR = 1.41; 95% CI = 1.01-1.98). Consumption of <500 g red meat per week or ≤125 total kcal/100 g solid food per day is a statistically significant protective factor in the overall cohort. Recommendations aimed at preventing all cancers also may reduce risk of highly aggressive prostate cancer.
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Two Novel Susceptibility Loci for Prostate Cancer in Men of African Ancestry.
Publication Type:
Article
Year of Publication:
2017
Author(s):
Conti DV, Wang K, Sheng X, Bensen JT, Hazelett DJ, Cook MB, Ingles SA, Kittles RA, Strom SS, Rybicki BA, Nemesure B, Isaacs, WB, Stanford JL, Zheng W, Sanderson M, John EM, Park JY, Xu J, Stevens VL, Berndt SI, Huff CD, Wang Z, Yeboah ED, Tettey Y, Biritwum RB, Adjei AA, Tay E, Truelove A, Niwa S, Sellers TA, Yamoah K, Murphy AB, Crawford DC, GapsturS M, Bush WS, Aldrich MC, Cussenot O, Petrovics G, Cullen J, Neslund-Dudas C, Stern MC, Kote-Jarai Z, Govindasami K, Chokkalingam AP, Hsing AW, Goodman PJ, Hoffmann T, Drake BF, Hu JJ, Clark PE, Van Den Eeden SK, Blanchet P, Fowke JH, Casey G, Hennis AJM, Han Y, Lubwama A, Thompson, Jr. IM, Leach R, Easton DF, Schumacher F, Van den Berg DJ, Gundell SM, Stram A, Wan P, Xia L, Pooler LC, Mohler JL, Fontham ETH, Smith GJ, Taylor JA, Srivastava S, Eeles RA, Kibel AS, Multigner L, Parent M-E, Menegaux F, Cancel-Tassin G, Klein EA, Brureau L, Stram DO, Watya S, Chanock SJ, Witte JS, Blot WJ, PRACTICAL/ELLIPSE Consortium, Henderson BE, Haiman CA.
Source:
J Natl Cancer Inst
Volume:
109
Issue:
8
Publication Date:
Aug 2017
Pagination:
1-5

Abstract

Prostate cancer incidence is 1.6-fold higher in African Americans than in other populations. The risk factors that drive this disparity are unknown and potentially consist of social, environmental, and genetic influences. To investigate the genetic basis of prostate cancer in men of African ancestry, we performed a genome-wide association meta-analysis using two-sided statistical tests in 10 202 case subjects and 10 810 control subjects. We identified novel signals on chromosomes 13q34 and 22q12, with the risk-associated alleles found only in men of African ancestry (13q34: rs75823044, risk allele frequency = 2.2%, odds ratio [OR] = 1.55, 95% confidence interval [CI] = 1.37 to 1.76, P = 6.10 × 10−12; 22q12.1: rs78554043, risk allele frequency = 1.5%, OR = 1.62, 95% CI = 1.39 to 1.89, P = 7.50 × 10−10). At 13q34, the signal is located 5’ of the gene IRS2 and 3’ of a long noncoding RNA, while at 22q12 the candidate functional allele is a missense variant in the CHEK2 gene. These findings provide further support for the role of ancestry-specific germline variation in contributing to population differences in prostate cancer risk.

The incidence of prostate cancer (PCa) in African American men is 1.6-fold higher than in other racial/ethnic populations (1), remaining one of the most important health disparities globally. Reasons for this disparity likely involve a multitude of factors, including social and environmental factors and inherited susceptibility. Genome-wide association studies (GWAS) have identified more than 100 common risk alleles for PCa (2–7), including the susceptibility region on chromosome 8q24, which harbors multiple variants that have been suggested to contribute to racial/ethnic differences in PCa risk (8,9).

To search for additional PCa risk variants in men of African ancestry that may contribute to their greater disease incidence, we combined genetic association results from the African Ancestry Prostate Cancer GWAS Consortium (AAPC; 4853 case subjects and 4678 control subjects) (9), the Ghana Prostate Study (474 case subjects and 458 control subjects) (10), the Kaiser/ProHealth Prostate Cancer Study (601 case subjects and 1650 control subjects) (11), and the ELLIPSE/PRACTICAL OncoArray Consortium (4274 case subjects and 4024 control subjects) (Supplementary Table 1, available online). Subjects provided written informed consent to participate in the study. The protocol and consent documents were approved by the institutional review boards at each of the participating institutions. A total of 17.8 million genotyped and imputed single nucleotide polymorphisms (SNPs) and insertion/deletion variants with frequencies of 1% or more were tested for an association with PCa risk. For each SNP, per-allele odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression, and we tested for allele dosage effects through a 1-degree of freedom Wald trend test. All statistical tests were two-sided. Results from each study were combined through a meta-analysis of 10 202 case subjects and 10 810 control subjects (Supplementary Methods, available online). The cut-point for genome-wide statistical significance was a P value of less than 5.00×10-8.

Only minor evidence of inflation in the test statistic was observed following adjustment for global genetic ancestry (λ = 1.04). In the meta-analysis, 775 alleles achieved genome-wide statistical significance (P < 5.00 × 10-8). These alleles were located at the 8q24 risk region (543 alleles) and other known susceptibility regions on chromosomes 2p15(EHBP1), 2q37(MLPH), 6q22(RFX6), 8p21(NKX3-1), 10q11(MSMB), 11q13(MYEOV), 12q13(KRT8), 17q21(ZNF652), and Xp11(NUDT11/LINC01496) (Supplementary Figure 1A, available online). Outside of these regions, genome-wide statistically significant associations were also observed on chromosomes 13q34 and 22q12.1 (Table 1; Supplementary Figure 1B, available online), with the risk-associated alleles found almost exclusively in men of African ancestry. At 13q34, marker rs75823044 (2.2% frequency) was associated with an odds ratio of 1.55 (95% CI = 1.37 to 1.76, P = 6.10×10-12). This marker is located within a cluster of five moderately correlated alleles (r2 > 0.30) approximately 45 kb 3’ of the gene insulin receptor substrate 2 (IRS-2), a signaling protein that mediates the effect of insulin and insulin-like growth factor 1 (12), and 20 kb 5’ of a long noncoding RNA (LINC00676). Of these five variants, rs151190668 (OR = 1.67, 95% CI = 1.43 to 1.96, P = 1.70×10-10) appears to be the best functional candidate because it is located in a region containing epigenetic chromatin modifications and androgen receptor and FOXA1 binding consistent with regulatory sequences (Figure 1; Supplementary Methods, available online).
Figure 1.
Figure 1.
Regional plot of a novel genome-wide statistically significant prostate cancer risk region at chromosome 13q34. Single nucleotide polymorphisms (SNPs) are plotted by their position 110 kb on either side of the index SNP (purple diamond) on the ...
Table 1.
Table 1.
Association results for prostate cancer risk variants at 13q34 and 22q12.1 in men of African ancestry

At 22q12.1, the association signal was also defined by multiple low-frequency African ancestry–specific variants spanning approximately 944 kb, with rs78554043 being the most statistically significant variant (1.5% frequency, OR = 1.62, 95% CI = 1.39 to 1.89, P = 7.50×10-10) (Table 1). The variant rs78554043 is correlated (r2 = 1) with a missense polymorphism (rs17886163, Ile448Ser, P = 1.38×10-9) in the CHEK2 gene (Supplementary Table 4, available online), which is a likely candidate for the underlying biologically functional allele. Although the Ile448Ser missense is characterized as “benign” by Polyphen2 and ClinVar and “tolerated” by Sifting Intolerant from Tolerant (SIFT) (Supplementary Methods, available online), it involves a nonconservative nonpolar to polar change in the amino acid. While the possibility of rare regulatory variation cannot be excluded, this nonconservative change provides support for previous studies suggesting that rare/less common missense variants in CHEK2 may be important in PCa development (13).

The risk alleles rs75823044 and rs78554043 are found almost exclusively in African ancestry populations. In the 1000 Genomes Project populations (n = 2504 subjects), the risk allele for rs75823044 was found in 48 of 661 African ancestry samples (AFR), one of 85 Peruvians, and one of 96 Punjabi. For rs78554043, the risk allele was found in 30 of 661 AFR samples, one of 104 Puerto Ricans, and one of 94 Colombians (data not shown).

At 13q34 and 22q12.1, no nominally statistically significant (P < .05) evidence of effect heterogeneity was noted by age (above vs below the median age in case subjects plus control subjects of 64, P ≥ .27) or disease aggressiveness (high-risk vs low-risk PCa, P ≥ .20) (Supplementary Methods, available online). GWAS of high-risk disease (vs controls) and high- (n = 2984) vs low-risk (n = 3012) disease (Supplementary Methods, available online) did not reveal any novel PCa loci of genome-wide statistical significance that could differentiate risk by disease aggressiveness (Supplementary Figure 1, C and D, available online). In addition, aside from 8q24 (14), admixture mapping using 220 474 genotyped SNPs in case-case and case-control comparisons of local ancestry (Supplementary Methods, available online) failed to identify any novel risk regions harboring risk alleles that are highly differentiated in frequency between men of African and European ancestry (data not shown) (Supplementary Figure 2A, available online).

The most statistically significant PCa risk association genome wide was observed with a novel triallelic (A/T/G) variant at 8q24, with the T allele found in approximately 12% of case subjects and approximately 6% of control subjects (rs72725854 at position 128,074,815 located in “region 2”) (8). The risk allele (T) is only found in populations of African ancestry with a per-allele odds ratio of 2.33 (95% CI = 2.16 to 2.50, P = 1.08×10-109) (Supplementary Figure 2B, available online) and is in linkage disequilibrium with African ancestry–specific risk alleles rs114798100 (4%, OR = 2.43, 95% CI = 2.21 to 2.66, P = 4.07×10-81) and rs111906932 (2%, OR = 1.92, 95% CI = 1.70 to 2.16, P = 1.44×10-26) (8,9). These SNPs are not correlated (r2 = 0 for rs114798100 and rs111906932) but define all observed haplotypes with the risk allele T of rs72725854, and thus describe the same association signal. In stepwise models, four additional variants were found to capture risk (P < 10-5) across the 8q24 locus (127.8–128.8 Mb) in men of African ancestry (Supplementary Table 2, available online).

Of the 100 reported PCa risk loci, 94 variants are polymorphic with an MAF of 0.05 or greater, 81 are directionally consistent with previous results in other populations (OR > 1), and 47 are nominally statistically significant associations (P < .05) in men of African ancestry (data not shown). Based on a polygenic risk score (Supplementary Methods, available online) comprising these risk variants as well as novel variants at 13q34 and 22q12.1 and variants shown to capture risk at 8q24 in men of African ancestry (n = 5), the 10% of men with the highest polygenic risk scores have a 3-fold (95% CI = 2.52 to 3.63) of PCa compared with men with “average risk” (polygenic risk scores in the 25th to 75th percentiles) (Supplementary Table 3, available online), which is comparable with that observed for the top 10% of the risk score distribution in men of European ancestry (OR = 2.93, 95% CI = 2.75 to 3.12) (2). Estimates for the top 1% of the polygenic risk scores in each population are 4.23 and 5.65, respectively.

A main limitation of this study is suboptimal statistical power (<80%) to detect modest effects (OR < 1.22) at genome-wide levels of statistical significance for common alleles with minor allele frequencies of less than 10%, particularly in analyses stratified by disease aggressiveness. Another limitation is the lack of understanding regarding the biological mechanisms through which genetic variation in these susceptibility regions influences risk.

Our findings substantiate the importance of conducting large-scale genetic studies in diverse populations for the discovery of novel risk loci that are ancestry specific (15). Further discovery efforts and fine-mapping of known loci will be needed to better understand the contribution of germline variation to PCa in men of African ancestry.
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Funding

This work was supported by the National Cancer Institute at the National Institutes of Health, ELLIPSE GAME-ON U19 initiative for prostate cancer (U19 CA148537).
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Notes

Authors: David V. Conti, Kan Wang, Xin Sheng, Jeannette T. Bensen, Dennis J. Hazelett, Michael B. Cook, Sue A. Ingles, Rick A. Kittles, Sara S. Strom, Benjamin A. Rybicki, Barbara Nemesure, William B. Isaacs, Janet L. Stanford, Wei Zheng, Maureen Sanderson, Esther M. John, Jong Y. Park, Jianfeng Xu, Victoria L. Stevens, Sonja I. Berndt, Chad D. Huff, Zhaoming Wang, Edward D. Yeboah, Yao Tettey, Richard B. Biritwum, Andrew A. Adjei, Evelyn Tay, Ann Truelove, Shelley Niwa, Thomas A. Sellers, Kosj Yamoah, Adam B. Murphy, Dana C. Crawford, Susan M. Gapstur, William S. Bush, Melinda C. Aldrich, Olivier Cussenot, Gyorgy Petrovics, Jennifer Cullen, Christine Neslund-Dudas, Mariana C. Stern, Zsofia-Kote Jarai, Koveela Govindasami, Anand P. Chokkalingam, Ann W. Hsing, Phyllis J. Goodman, Thomas Hoffmann, Bettina F. Drake, Jennifer J. Hu, Peter E. Clark, Stephen K. Van Den Eeden, Pascal Blanchet, Jay H. Fowke, Graham Casey, Anselm J. M. Hennis, Ying Han, Alexander Lubwama, Ian M. Thompson, Jr, Robin Leach, Douglas F. Easton, Fredrick Schumacher, David J. Van den Berg, Susan M. Gundell, Alex Stram, Peggy Wan, Lucy Xia, Loreall C. Pooler, James L. Mohler, Elizabeth T. H. Fontham, Gary J. Smith, Jack A. Taylor, Shiv Srivastava, Rosalind A. Eeles, John Carpten, Adam S. Kibel, Luc Multigner, Marie-Elise Parent, Florence Menegaux, Geraldine Cancel-Tassin, Eric A. Klein, Laurent Brureau, Daniel O. Stram, Stephen Watya, Stephen J. Chanock, John S. Witte, William J. Blot, Brian E. Henderson†, Christopher A. Haiman; for the PRACTICAL/ELLIPSE Consortium

†Deceased.

Affiliations of authors: Department of Preventive Medicine (DVC, KW, XS, SAI, MCS, YH, DJVdB, SMG, AS, PW, LX, LCP, DOS, BEH, CAH) and Department of Translational Genomics (JC), Keck School of Medicine, and Norris Comprehensive Cancer Center (SAI, MCS, DOS, BEH, CAH), University of Southern California, Los Angeles, CA; Department of Epidemiology (JTB) and Lineberger Comprehensive Cancer Center (JTB, JLM), University of North Carolina at Chapel Hill, Chapel Hill, NC; Bioinformatics and Computational Biology Research Center, Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA (DJH); Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD (MBC, SIB, SJC); University of Arizona College of Medicine and University of Arizona Cancer Center, Tucson, AZ (RAK); Department of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, TX (SSS, CDH); Department of Public Health Sciences, Henry Ford Hospital, Detroit, MI (BAR, CND); Department of Preventive Medicine, Stony Brook University, Stony Brook, NY (BN, AJMH); James Buchanan Brady Urological Institute, Johns Hopkins Hospital and Medical Institution, Baltimore, MD (WBI); Division of Public Health Sciences (JLS) and SWOG Statistical Center (PJG), Fred Hutchinson Cancer Research Center, Seattle, WA; Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA (JLS); Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, TN (WZ, WJB); Department of Family and Community Medicine, Meharry Medical College, Nashville, TN (MS); California Prevention Institute of California, Fremont, CA (EMJ); Department of Health Research and Policy (Epidemiology) (EMJ) and Department of Medicine (AWH), Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA; Department of Cancer Epidemiology (JYP, TAS) and Department of Radiation Oncology and Cancer Epidemiology (KY), Moffitt Cancer Center and Research Institute, Tampa, FL; Program for Personalized Cancer Care and Department of Surgery, NorthShore University HealthSystem, Evanston, IL (JX); Epidemiology Research Program, American Cancer Society, Atlanta, GA (VLS, SMG); Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN (ZW); University of Ghana Medical School, Accra, Ghana (EDY, YT, RBB, AAA, ET); Korle Bu Teaching Hospital, Accra, Ghana (EDY, YT, RBB, AAA, ET); Westat, Rockville, MD (AT, SN); Department of Urology, Northwestern University, Chicago, IL (ABM); Institute for Computational Biology, Department of Epidemiology and Biostatistics (DCC, WSB) and Department of Epidemiology and Biostatistics (FS), Case Western Reserve University, Cleveland, OH (DCC, WSB); Division of Epidemiology, Department of Thoracic Surgery (MCA) and Department of Medicine and Urologic Surgery (JHF), Vanderbilt University Medical Center (PEC), Nashville, TN; CeRePP, GRC No. 5 ONCOTYPE-URO, Institut Universitaire de Cancérologie, UPMC Univ Paris 6, Paris, France (OC, GCT); Department of Surgery, Center for Prostate Disease Research, Uniformed Services University of the Health Sciences, Bethesda, MD (GP, JC, SS); The Institute of Cancer Research, Sutton, London, UK (ZKJ, RAE); Oncogenetics Team, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Sutton, UK (KG); School of Public Health, University of California, Berkeley, Berkeley, CA (APC); Department of Epidemiology and Biostatistics (TH, JSW) and Institute for Human Genetics (JSW), University of California, San Francisco, CA (TH, JSW); Department of Surgery, Division of Public Health Sciences, Washington University School of Medicine, St. Louis, MO (BFD); Sylvester Comprehensive Cancer Center and Department of Public Health Sciences, University of Miami Miller School of Medicine, Miami, FL (JJH); Division of Research, Kaiser Permanente Northern California, Oakland, CA (SKVDE); University Hospital of Pointe-à-Pitre, Guadeloupe (PB, LB); FWI and Inserm U1085-IRSET, Rennes, France (PB, LB); French West Indies University, Pointe-à-Pitre, Guadeloupe, FWI (PB, LB); Center for Public Health Genomics, Department of Public Health Sciences, University of Virginia, Charlottesville, VA (GC); Chronic Disease Research Centre and Faculty of Medical Sciences, University of the West Indies, Bridgetown, Barbados (AJMH); School of Public Health, Makerere University College of Health Sciences, Kampala, Uganda (AL, SW); Department of Urology, University of Texas Health Science Center at San Antonio, San Antonio, TX (IMTJr, RL); Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK (DFE); Department of Urology, Roswell Park Cancer Institute, Buffalo, NY (JLM, GJS); School of Public Health, Louisiana State University Health Sciences Center, New Orleans, LA (ETHF); Epigenetic and Stem Cell Biology Laboratory and Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC (JAT); Royal Marsden NHS Foundation Trust, London, UK (RAE); Division of Urology, Brigham and Women's Hospital/Dana-Farber Cancer Institute, Boston, MA (ASK); Washington University, St. Louis, MO (ASK); Inserm U1085 – IRSET, Rennes, France (LM); INRS-Institut Armand-Frappier, Institut National de la Recherche Scientifique, University of Quebec, Laval, Quebec, Canada (MEP); Inserm, Team Cancer-Environment, Center for Research in Epidemiology and Population Health, Université Paris-Saclay, Université Paris-Sud, Villejuif, France (FM); Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH (EAK); Uro Care, Kampala, Uganda (SW).

Additional members and affiliations appear in the Supplementary Note (available online).

This study is dedicated to the memory of Brian E. Henderson.

The study funders had no role in the design of the study; the collection, analysis, or interpretation of the data; the writing of the manuscript; or the decision to submit the manuscript for publication.

A full listing of acknowledgements is detailed in the Supplementary Methods (available online).
Go to:
Supplementary Material
Supplementary Data
Click here for additional data file.(1.0M, docx)
Go to:
Notes

This paper was supported by the following grant(s):
National Cancer Institute at the National Institutes of Health U19CA148537.
Go to:
References
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Articles from JNCI Journal of the National Cancer Institute are provided here courtesy of Oxford University Press
Show Abstract

The Association of Diabetes and Obesity with Prostate Cancer Progression: HCaP-NC
Publication Type:
Article
Year of Publication:
2017
Author(s):
Khan S, Cai J, Nielsen ME, Troester MA, Mohler JL, Fontham ETH, Hendrix LH, Farnan L, Olshan AF, Bensen JT.
Source:
Prostate
Volume:
77
Issue:
8
Publication Date:
June 1, 2017
Pagination:
878-887

Abstract

BACKGROUND. The role of race in modifying the association among diabetes, obesity, and
prostate cancer (CaP) progression is not well studied. We evaluated diabetes and obesity in
association with time to CaP progression in White Americans (Whites) and Black Americans
(Blacks).

METHODS. Our study sample consisted of 363 White and 284 Black research participants
from the Health Care Access and CaP Treatment in North Carolina (HCaP-NC) cohort. The
association between self-reported diabetes or obesity and CaP progression (mean follow-up
time approximately 5 years) was assessed using Cox proportional hazards modeling, with
adjustment for potential confounders. Stratum-specific hazard ratio (HR) estimates for
Whites and Blacks were evaluated.

RESULTS. Self-reported diabetes was not associated with CaP progression in the cohort as a
whole (HR: 0.86, 95%CI: 0.54, 1.35), or among racially defined groups (Whites, HR: 1.03, 95%
CI: 0.50, 2.13 or Blacks, HR: 0.77, 95%CI: 0.43, 1.39). Obesity was positively associated with
CaP progression among Whites, in models including (HR: 1.79, 95%CI: 1.08, 2.97), and excluding (HR: 1.80, 95%CI: 1.09, 2.96) diabetes as a covariate. No association was observed
between obesity and CaP progression in Blacks or the cohort as whole.

CONCLUSIONS. Self-reported diabetes was not associated with CaP progression In HCaPNC.
Obesity was associated with CaP progression only among White research participants
Show Abstract

Unit Nonresponse in a Population-Based Study of Prostate Cancer.
Publication Type:
Article
Year of Publication:
2016
Author(s):
Oral E, Simonsen N, Brennan C, Berken J, Su LJ, Mohler JL, et al.
Source:
The Prostate
Volume:
11
Issue:
12
Publication Date:
December 16, 2016
Pagination:
e0168364

Abstract

Low unit response rates can increase bias and compromise study validity. Response rates have continued to fall over the past decade despite all efforts to increase participation. Many factors have been linked to reduced response, yet relatively few studies have employed multivariate approaches to identify characteristics that differentiate respondents from nonrespondents since it is hard to collect information on the latter. We aimed to assess factors contributing to enrollment of prostate cancer (PCa) patients. We combined data from the North Carolina-Louisiana (LA) PCa Project’s LA cohort, with additional sources such as US census tract and LA tumor registry data. We included specific analyses focusing on blacks, a group often identified as hard to enroll in health-related research. The ability to study the effect of Hurricane Katrina, which occurred amidst enrollment, as a potential determinant of nonresponse makes our study unique. Older age (≥ 70) for blacks (OR 0.65) and study phase with respect to Hurricane Katrina for both races (OR 0.59 for blacks, OR 0.48 for whites) were significant predictors of participation with lower odds. Neighborhood poverty for whites (OR 1.53) also was a significant predictor of participation, but with higher odds. Among blacks, residence in Orleans parish was associated with lower odds of participation (OR 0.33) before Katrina. The opposite occurred in whites, with lower odds (OR 0.43) after Katrina. Our results overall underscore the importance of tailoring enrollment approaches to specific target population characteristics to confront the challenges posed by nonresponse. Our results also show that recruitment-related factors may change when outside forces bring major alterations to a population's environment and demographics.
Show Abstract

Saturated fat intake and prostate cancer aggressiveness: results from the population-based North Carolina-Louisiana Prostate Cancer Project.
Publication Type:
Article
Year of Publication:
2017
Author(s):
Allott EH, Arab L, Su LJ, Farnan L, Fontham ET, Mohler JL, Bensen JT, Steck SE. Epub 2016 Sep 6. doi: 10.1038/pcan.2016.39. PubMed PMID: 27595916.
Source:
Prostate Cancer Prostatic Dis.
Volume:
20
Issue:
1
Publication Date:
Mar 2017
Pagination:
48-53

Abstract

BACKGROUND: Epidemiologic and laboratory evidence supports a role for cholesterol in prostate cancer (PC). Dietary saturated fat content impacts serum cholesterol levels. However, epidemiologic associations between saturated fat and PC aggressiveness are inconsistent. We hypothesized that high saturated fat intake would be associated with increased PC aggressiveness, and that statin use would modify this association.

METHODS: Of 1854 PC cases in the North Carolina-Louisiana PC Project, 321 (17%) were classified as high aggressive (Gleason sum ⩾8, PSA>20 ng ml-1, or Gleason sum ⩾7 and clinical stage T3-4) or low/intermediate aggressive (all other cases). Using low/intermediate aggressive cases as the referent group, we examined the association between tertiles of total fat-adjusted saturated fat intake and high aggressive PC using logistic regression, overall and stratified by race and statin use. We examined total fat-adjusted polyunsaturated and monounsaturated fatty acids (PUFA and MUFA, respectively), trans fat and cholesterol intake in secondary analysis.

RESULTS: High total fat-adjusted saturated fat intake was associated with an elevated odds ratio (OR) for aggressive PC (ORT3vsT1 1.51; 95% CI 1.10-2.06; P-trend=0.009), with an attenuated association in statin users (ORT3vsT1 1.16; 95% CI 0.67-2.01; P-trend=0.661) compared with non-users (ORT3vsT1 1.71; 95% CI 1.16-2.51; P-trend=0.053). High total fat-adjusted cholesterol intake was associated with aggressive PC in European Americans (ORT3vsT1 1.62; 95% CI 1.02-2.58; P-trend=0.056), but not African Americans (ORT3vsT1 0.92; 95% CI 0.60-1.42; P-trend=0.750). High total fat-adjusted PUFA was inversely associated with PC aggressiveness (ORT3vsT1 0.75; 95% CI 0.55-1.03), although this was not significant. No associations were found between total fat-adjusted MUFA or trans fat and PC aggressiveness.

CONCLUSIONS: High total fat-adjusted saturated fat intake was associated with increased PC aggressiveness, with a suggestion of a stronger effect in men not using statins. The association between total fat-adjusted cholesterol intake and PC aggressiveness was most pronounced in European Americans.
Show Abstract

Quality of care received and patient-reported regret in prostate cancer: Analysis of a population-based prospective cohort.
Publication Type:
Article
Year of Publication:
2016
Author(s):
Holmes JA, Bensen JT, Mohler JL, Song L, Mishel MH, Chen RC.
Source:
Cancer
Volume:
123
Issue:
1
Publication Date:
Jan. 1 2017
Pagination:
138-143

Abstract

BACKGROUND:

Meeting quality of care standards in oncology is recognized as important by physicians, professional organizations, and payers. Data from a population-based cohort of patients with prostate cancer were used to examine whether receipt of care was consistent with published consensus metrics and whether receiving high-quality care was associated with less patient-reported treatment decisional regret.
METHODS:

Patients with incident prostate cancer were enrolled in collaboration with the North Carolina Central Cancer Registry, with an oversampling of minority patients. Medical record abstraction was used to determine whether participants received high-quality care based on 5 standards: 1) discussion of all treatment options; 2) complete workup (prostate-specific antigen, Gleason grade, and clinical stage); 3) low-risk participants did not undergo a bone scan; 4) high-risk participants treated with radiotherapy (RT) received androgen deprivation therapy; and 5) participants treated with RT received conformal or intensity-modulated RT. Treatment decisional regret was assessed using a validated instrument.
RESULTS:

A total of 804 participants were analyzed. Overall, 66% of African American and 73% of white participants received care that met all standards (P = .03); this racial difference was confirmed by multivariable analysis. Care that included "discussion of all treatment options" was found to be associated with less patient-reported regret on univariable analysis (P = .03) and multivariable analysis (odds ratio, 0.59; 95% confidence interval, 0.37-0.95).
CONCLUSIONS:

The majority of participants received high-quality care, but racial disparity existed. Participants who discussed all treatment options appeared to have less treatment decisional regret. To the authors' knowledge, this is the first study to demonstrate an association between a quality of care metric and patient-reported outcome. Cancer 2017;138-143. © 2016 American Cancer Society.

KEYWORDS:

patient-reported outcomes; prostate cancer; quality of care; racial disparities; regret
Show Abstract

The association of diabetes and obesity with prostate cancer aggressiveness among Black Americans and White Americans in a population-based study
Publication Type:
Article
Year of Publication:

Author(s):
Khan S, Cai J, Nielsen ME, Troester MA, Mohler JL, Fontham ET, Hendrix LH, Farnan L, Olshan AF, Bensen JT
Source:
Cancer Causes Control
Volume:
27
Issue:
12
Publication Date:
December 2016
Pagination:
1475-1485

Abstract

PURPOSE: Few studies have investigated the role of race in the association of diabetes and obesity with prostate cancer aggressiveness. Here we evaluate the independent association between diabetes and obesity with prostate cancer aggressiveness in White Americans and Black Americans.

METHODS: Our cross-sectional, case-only study consisted of 1,058 White Americans and 991 Black Americans from the North Carolina-Louisiana Prostate Cancer (PCaP) project. Diabetes status was determined by self-report. Obesity was determined using body mass index and calculated based on anthropometric measurements. High aggressive prostate cancer was defined as Gleason sum ≥8, or prostate-specific antigen >20 ng/ml, or Gleason sum = 7 and clinical stage cT3-cT4. The association between diabetes and obesity with high aggressive prostate cancer at diagnosis was evaluated using multivariable logistic regression and adjusted for potential confounders.

RESULTS: Diabetes was not associated with high aggressive prostate cancer in the overall sample (OR 1.04; 95% CI 0.79, 1.37), White Americans (OR 1.00; 95% CI 0.65, 1.57) or Black Americans (OR 1.07; 95% CI 0.75, 1.53). Obesity, independent of diabetes, was positively associated with high aggressive prostate cancer in White Americans (OR 1.98; 95% CI 1.14, 3.43), but not in the overall sample (OR 1.37; 95% CI 0.99, 1.92) or Black Americans (OR 1.09; 95% CI 0.71, 1.67).

CONCLUSIONS: Diabetes was not associated with prostate cancer aggressiveness, overall, or in either race group. Obesity, independent of diabetes, was associated with high aggressive prostate cancer only in White Americans.
Show Abstract

Carotenoid intake and adipose tissue carotenoid levels in relation to prostate cancer aggressiveness among African-American and European-American men in the North Carolina-Louisiana prostate cancer project (PCaP).
Publication Type:
Article
Year of Publication:
2016
Author(s):
Antwi SO, Steck SE, Su LJ, Hebert JR, Zhang H, Craft NE, Fontham ET, Smith GJ, Bensen JT, Mohler JL, Arab L.
Source:
The Prostate
Volume:
76
Issue:
12
Publication Date:
Sep 2016
Pagination:
1053-66

Abstract

BACKGROUND:

Associations between carotenoid intake and prostate cancer (CaP) incidence have varied across studies. This may result from combining indolent with aggressive disease in most studies. This study examined whether carotenoid intake and adipose tissue carotenoid levels were inversely associated with CaP aggressiveness.

METHODS:

Data on African-American (AA, n = 1,023) and European-American (EA, n = 1,079) men with incident CaP from North Carolina and Louisiana were analyzed. Dietary carotenoid intake was assessed using a detailed-food frequency questionnaire (FFQ), and abdominal adipose tissue samples were analyzed for carotenoid concentrations using high-performance liquid chromatography. Multivariable logistic regression was used in race-stratified analyses to calculate odds ratios (ORs) and 95% confidence intervals (95%CI) comparing high aggressive CaP with low/intermediate aggressive CaP.

RESULTS:

Carotenoid intake differed significantly between AAs and EAs, which included higher intake of lycopene among EAs and higher β-cryptoxanthin intake among AAs. Comparing the highest and lowest tertiles, dietary lycopene was associated inversely with high aggressive CaP among EAs (OR = 0.55, 95%CI: 0.34-0.89, Ptrend  = 0.02), while an inverse association was observed between dietary β-cryptoxanthin intake and high aggressive CaP among AAs (OR = 0.56, 95%CI: 0.36-0.87, Ptrend  = 0.01). Adipose tissue α-carotene and lycopene (cis + trans) concentrations were higher among EAs than AAs, and marginally significant inverse linear trends were observed for adipose α-carotene (Ptrend  = 0.07) and lycopene (Ptrend  = 0.11), and CaP aggressiveness among EAs only.

CONCLUSIONS:

These results suggest that diets high in lycopene and β-cryptoxanthin may protect against aggressive CaP among EAs and AAs, respectively. Differences in dietary behaviors may explain the observed racial differences in associations.

adipose tissue; carotenoids; lutein; lycopene; nutritional biomarkers; prostate cancer; supplements; zeaxanthin; α−carotene; β−carotene; β−cryptoxanthin
Show Abstract

Genome-wide association studies in women of African ancestry identified 3q26.21 as a novel susceptibility locus for oestrogen receptor negative breast cancer.
Publication Type:
Article
Year of Publication:
2016 Nov 1.
Author(s):
Huo D, Feng Y, Haddad S, Zheng Y, Yao S, Han YJ, Ogundiran TO, Adebamowo C, Ojengbede O, Falusi AG, Zheng W, Blot W, Cai Q, Signorello L, John EM, Bernstein L, Hu JJ, Ziegler RG, Nyante S, Bandera EV, Ingles SA, Press MF, Deming SL, Rodriguez-Gil JL, Nathanson KL, Domchek SM, Rebbeck TR, Ruiz-Narváez EA, Sucheston-Campbell LE, Bensen JT, Simon MS, Hennis A, Nemesure B, Leske MC, Ambs S, Chen LS, Qian F, Gamazon ER, Lunetta KL, Cox NJ, Chanock SJ, Kolonel LN, Olshan AF, Ambrosone CB, Olopade OI, Palmer JR, Haiman CA.
Source:
Hum Mol Genet.
Volume:
25
Issue:
21
Publication Date:
Nov. 1 2016
Pagination:
4835-4846

Abstract

Multiple breast cancer loci have been identified in previous genome-wide association studies, but they were mainly conducted in populations of European ancestry. Women of African ancestry are more likely to have young-onset and oestrogen receptor (ER) negative breast cancer for reasons that are unknown and understudied. To identify genetic risk factors for breast cancer in women of African descent, we conducted a meta-analysis of two genome-wide association studies of breast cancer; one study consists of 1,657 cases and 2,029 controls genotyped with Illumina's HumanOmni2.5 BeadChip and the other study included 3,016 cases and 2,745 controls genotyped using Illumina Human1M-Duo BeadChip. The top 18,376 single nucleotide polymorphisms (SNP) from the meta-analysis were replicated in the third study that consists of 1,984 African Americans cases and 2,939 controls. We found that SNP rs13074711, 26.5 Kb upstream of TNFSF10 at 3q26.21, was significantly associated with risk of oestrogen receptor (ER)-negative breast cancer (odds ratio [OR]=1.29, 95% CI: 1.18-1.40; P = 1.8 × 10 -  8). Functional annotations suggest that the TNFSF10 gene may be involved in breast cancer aetiology, but further functional experiments are needed. In addition, we confirmed SNP rs10069690 was the best indicator for ER-negative breast cancer at 5p15.33 (OR = 1.30; P = 2.4 × 10 -  10) and identified rs12998806 as the best indicator for ER-positive breast cancer at 2q35 (OR = 1.34; P = 2.2 × 10 -  8) for women of African ancestry. These findings demonstrated additional susceptibility alleles for breast cancer can be revealed in diverse populations and have important public health implications in building race/ethnicity-specific risk prediction model for breast cancer.
Show Abstract

Dietary Total Antioxidant Capacity is Inversely Associated with Prostate Cancer Aggressiveness in a Population-Based Study.
Publication Type:
Article
Year of Publication:
2016
Author(s):
Vance TM, Wang Y, Su LJ, Fontham ET, Steck SE, Arab L, Bensen JT, Mohler JL, Chen MH, Chun OK.
Source:
Nutr Cancer
Volume:
68
Issue:
2
Publication Date:
Feb-Mar 2016
Pagination:
214-24

Abstract

The purpose of this study was to determine the relationship between total antioxidant capacity (TAC) from diet and supplements and prostate cancer aggressiveness among 855 African Americans (AA) and 945 European Americans (EA) in the North Carolina-Louisiana Prostate Cancer Project (PCaP). Cases were classified as either high aggressive, low aggressive, or intermediate aggressive. TAC was calculated from the vitamin C equivalent antioxidant capacity of 42 antioxidants measured via food frequency questionnaire. EA reported greater dietary TAC from diet and supplements combined (P < 0.0001). In both minimally and fully adjusted logistic regression models, TAC from diet and supplements combined was associated with a reduced odds of high aggressive prostate cancer in all men, AA and EA: odds ratios for highest vs. lowest level (>1500 vs. <500 mg vitamin C equivalent/day): 0.31 [95% confidence interval (CI): 0.15, 0.67; P-trend < 0.01], 0.28 (95% CI: 0.08, 0.96; P-trend < 0.001), and 0.36 (95% CI: 0.15, 0.86; P-trend = 0.58), respectively. These associations did not appear to differ between AA and EA. These data suggest that greater intake of antioxidants is associated with less aggressive prostate cancer. Additional research is needed to confirm these results and determine the underlying mechanisms.
Show Abstract

Statin Use and Prostate Cancer Aggressiveness: Results from the Population-Based North Carolina-Louisiana Prostate Cancer Project.
Publication Type:
Article
Year of Publication:
2016
Author(s):
Allott EH, Farnan L, Steck SE, Arab L, Su LJ, Mishel M, Fontham ET, Mohler JL, Bensen JT.
Source:
Cancer Epidemiol Biomarkers Prev.
Volume:
25
Issue:
4
Publication Date:
April 2016
Pagination:
670-7

Abstract

BACKGROUND:

Although statin use has been associated with reduced prostate cancer aggressiveness, the impact of race and patient characteristics on this association is not well understood. We examined the association between statin use and prostate cancer aggressiveness in Caucasians (CA) and African Americans (AA) and explored effect modification by health-seeking behaviors associated with statin use.

METHODS:

Of 1,930 cases from The North Carolina-Louisiana Prostate Cancer Project, 344 (18%) were classified as aggressive based on clinical criteria. Utilizing nonaggressive cases as referent, logistic regression was used to examine the association between statin use and prostate cancer aggressiveness, overall and stratified by race. Smoking and prostate cancer screening were examined as effect modifiers of this association.

RESULTS:

There was an inverse association between statin use and prostate cancer aggressiveness [OR, 0.74; 95% confidence interval (CI), 0.56-0.96], with comparable effect estimates in both races. Although not statistically significant, statin use was associated with reduced ORs for aggressive prostate cancer in never-screened men (OR, 0.79; 95% CI, 0.45-1.39), men screened at low/recommended frequency (≤once/year; OR, 0.66; 95% CI, 0.41-1.06), and men screened at high frequency (>once/year; OR, 0.78; 95% CI, 0.53-1.15). Inverse associations between statins and aggressive prostate cancer were strongest in never smokers (OR, 0.42; 95% CI, 0.25-0.72), attenuated in former smokers (OR, 0.84; 95% CI, 0.59-1.19), and absent in current smokers (OR, 1.36; 95% CI, 0.70-2.64).

CONCLUSIONS:

Statin use was associated with reduced prostate cancer aggressiveness in CA and AAs, with strongest inverse associations in nonsmokers.

IMPACT:

Health-seeking behaviors associated with statin use should be considered when examining the impact of statins on prostate cancer aggressiveness. Cancer Epidemiol Biomarkers Prev; 25(4); 670-7. ©2016 AACR.
Show Abstract

Intake of dietary antioxidants is inversely associated with biomarkers of oxidative stress among men with prostate cancer.
Publication Type:
Article
Year of Publication:
2016
Author(s):
Vance TM, Azabdaftari G, Pop EA, Lee SG, Su LJ, Fontham ET, Bensen JT, Steck SE, Arab L, Mohler JL, Chen MH, Koo SI, Chun OK.
Source:
Br J Nutr.
Volume:
115
Issue:
1
Publication Date:
January 14, 2016
Pagination:
68-74

Abstract

Prostate cancer is the most common non-cutaneous cancer and the second leading cause of cancer-related mortality among men in the USA. Growing evidence suggests that oxidative stress is involved in the development and progression of prostate cancer. In this study, the association between antioxidants from diet and supplements and biomarkers of oxidative stress in blood (n 278), urine (n 298) and prostate tissue (n 55) were determined among men from the North Carolina-Louisiana Prostate Cancer Project. The association between antioxidant intake and oxidative stress biomarkers in blood and urine was determined using linear regression, adjusting for age, race, prostate cancer aggressiveness and smoking status. Greater antioxidant intake was found to be associated with lower urinary 8-isoprostane concentrations, with a 10% increase in antioxidant intake corresponding to an unadjusted 1·1% decrease in urinary 8-isoprostane levels (95% CI -1·7, -0·3%; P value<0·01) and an adjusted 0·6% decrease (95% CI -1·4, 0·2%; P value=0·16). In benign prostate tissue, thioredoxin 1 was inversely associated with antioxidant intake (P=0·02). No significant associations were found for other blood or urinary biomarkers or for malignant prostate tissue. These results indicate that antioxidant intake may be associated with less oxidative stress among men diagnosed with prostate cancer.

KEYWORDS: Antioxidants; Diets; Oxidative stress; PCaP North Carolina-Louisiana Prostate Cancer Project; Prostate cancer; Trx1 thioredoxin 1
Show Abstract

Dietary, supplement, and adipose tissue tocopherol levels in relation to prostate cancer aggressiveness among African and European Americans: The North Carolina-Louisiana Prostate Cancer Project (PCaP).
Publication Type:
Article
Year of Publication:
2015
Author(s):
Antwi SO, Steck SE, Su LJ, Hébert JR, Zhang H, Fontham ET, Smith GJ, Bensen JT, Mohler JL, Arab L.
Source:
Prostate
Volume:
75
Issue:
13
Publication Date:
September 2016
Pagination:
1419-35

Abstract

BACKGROUND:

Controversies remain over the safety and efficacy of vitamin E (i.e., α-tocopherol) supplementation use for the prevention of prostate cancer (CaP); however, associations of different tocopherol forms and CaP aggressiveness have yet to be examined.

METHODS:

This study examined whether food intake of tocopherols, vitamin E supplement use, and adipose tissue biomarkers of tocopherol were associated with CaP aggressiveness among African-American (AA, n = 1,023) and European-American (EA, n = 1,079) men diagnosed with incident CaP. Dietary tocopherols were estimated from a food frequency questionnaire, supplement use from questionnaire/inventory, and biomarkers from abdominal adipose samples measured using high-performance liquid chromatography. Odds ratios (ORs) and 95% confidence intervals (95%CIs) were estimated from logistic regression comparing high-aggressive CaP to low/intermediate aggressive CaP, adjusting for covariates.

RESULTS:

Dietary intakes of α-and δ-tocopherol were related inversely to CaP aggressiveness among EAs [OR (95%CI), highest versus lowest quartile: α-tocopherol, 0.34 (0.17-0.69), P(trend)  = 0.006; δ-tocopherol, 0.45 (0.21-0.95) P(trend)  = 0.007]. Inverse associations between dietary and supplemental α-tocopherol and CaP aggressiveness were observed among AAs, though these did not reach statistical significance [OR (95%CI), highest versus lowest quartile: dietary α-tocopherol, 0.58 (0.28-1.19), P(trend)  = 0.20; supplemental α-tocopherol, 0.64 (0.31-1.21) P(trend)  = 0.15]. No significant association was observed between adipose tocopherol levels and CaP aggressiveness [OR (95%CI), highest versus lowest quartiles of α-tocopherol for EAs 1.43 (0.66-3.11) and AAs 0.66 (0.27-1.62)].
CONCLUSIONS:

The inverse associations observed between dietary sources of tocopherols and CaP aggressiveness suggests a beneficial role of food sources of these tocopherols in CaP aggressiveness.

KEYWORDS: adipose tissue; diet; nutritional biomarkers; prostate cancer; supplement; tocopherols; vitamin E
Show Abstract

Treatment decisional regret among men with prostate cancer: Racial differences and influential factors in the North Carolina Health Access and Prostate Cancer Treatment Project (HCaP-NC).
Publication Type:
Article
Year of Publication:
2015
Author(s):
Morris BB, Farnan L, Song L, Addington EL, Chen RC, Nielsen ME, Mishel M, Mohler JL, Bensen JT.
Source:
Cancer
Volume:
121
Issue:
12
Publication Date:
June 15, 2015
Pagination:
2029-35

Abstract

BACKGROUND:

It has been demonstrated that treatment decisional regret affects quality of life in patients with prostate cancer (CaP); however, there are limited studies that identify factors associated with treatment decisional regret, particularly within a racially diverse patient population that has extended follow-up.

METHODS:

Logistic regression analysis was used to determine associations between decisional regret and potential predictors in a population-based cohort of 348 African American men and 446 Caucasian American men approximately 3 years after CaP diagnosis.

RESULTS:

Of 794 research participants, 12% experienced treatment decisional regret. Decisional regret was associated with androgen-deprivation therapy (odds ratio [OR], 2.1; 95% confidence interval [CI], 1.1-4.0), recent urinary bother (OR, 3.4; 95% CI, 1.6-7.3), satisfaction with understanding potential treatment side effects (very unsatisfied: OR, 13.3; 95% CI, 5.5-32.2; somewhat unsatisfied: OR, 5.0; 95% CI, 2.3-11.2; neutral: OR, 3.8; 95% CI, 1.9-7.6), and CaP treatment effect on the spousal relationship (very affected: OR, 3.9; 95% CI, 2.0-7.6; somewhat affected: OR, 3.1; 95% CI, 1.4-7.3; neutral: OR, 2.4; 95% CI, 1.9-7.6). Younger African Americans were more likely to experience regret than older African Americans (OR, 3.0; 95% CI, 1.1-8.1), and older African Americans were less likely to experience regret than older Caucasian Americans (OR, 0.2; 95% CI, 0.1-0.7).

CONCLUSIONS:

Treatment decisional regret remains an important issue in CaP survivors beyond initial treatment. Potential interventions should involve younger African Americans and patient spouses. Increased regret may reflect the unexpected influence of treatment side effects on the patient's everyday life; helping the patient relate potential side effects to his individual situation could improve patient satisfaction.

KEYWORDS: African Americans; emotions; health status disparities; prostatic neoplasms; quality of life; spouses
Show Abstract

Associations of prostate cancer risk variants with disease aggressiveness: results of the NCI-SPORE Genetics Working Group analysis of 18,343 cases.
Publication Type:
Article
Year of Publication:
2015
Author(s):
Helfand BT, Roehl KA, Cooper PR, McGuire BB, Fitzgerald LM, Cancel-Tassin G, Cornu JN, Bauer S, Van Blarigan EL, Chen X, Duggan D, Ostrander EA, Gwo-Shu M, Zhang ZF, Chang SC, Jeong S, Fontham ET, Smith G, Mohler JL, Berndt SI, McDonnell SK, Kittles R, Rybicki BA, Freedman M, Kantoff PW, Pomerantz M, Breyer JP, Smith JR, Rebbeck TR, Mercola D, Isaacs WB, Wiklund F, Cussenot O, Thibodeau SN, Schaid DJ, Cannon-Albright L, Cooney KA, Chanock SJ, Stanford JL, Chan JM, Witte J, Xu J, Bensen JT, Taylor JA, Catalona WJ.
Source:
Hum Genet.
Volume:
134
Issue:
4
Publication Date:
April 2015
Pagination:
439-50

Abstract

Genetic studies have identified single nucleotide polymorphisms (SNPs) associated with the risk of prostate cancer (PC). It remains unclear whether such genetic variants are associated with disease aggressiveness. The NCI-SPORE Genetics Working Group retrospectively collected clinicopathologic information and genotype data for 36 SNPs which at the time had been validated to be associated with PC risk from 25,674 cases with PC. Cases were grouped according to race, Gleason score (Gleason ≤ 6, 7, ≥ 8) and aggressiveness (non-aggressive, intermediate, and aggressive disease). Statistical analyses were used to compare the frequency of the SNPs between different disease cohorts. After adjusting for multiple testing, only PC-risk SNP rs2735839 (G) was significantly and inversely associated with aggressive (OR = 0.77; 95 % CI 0.69-0.87) and high-grade disease (OR = 0.77; 95 % CI 0.68-0.86) in European men. Similar associations with aggressive (OR = 0.72; 95 % CI 0.58-0.89) and high-grade disease (OR = 0.69; 95 % CI 0.54-0.87) were documented in African-American subjects. The G allele of rs2735839 was associated with disease aggressiveness even at low PSA levels (<4.0 ng/mL) in both European and African-American men. Our results provide further support that a PC-risk SNP rs2735839 near the KLK3 gene on chromosome 19q13 may be associated with aggressive and high-grade PC. Future prospectively designed, case-case GWAS are needed to identify additional SNPs associated with PC aggressiveness.
Show Abstract

Association between Plasma 25-Hydroxyvitamin D, Ancestry and Aggressive Prostate Cancer among African Americans and European Americans in PCaP.
Publication Type:
Article
Year of Publication:
2015
Author(s):
Steck SE, Arab L, Zhang H, Bensen JT, Fontham ET, Johnson CS, Mohler JL, Smith GJ, Su JL, Trump DL, Woloszynska-Read A.
Source:
PLoS One
Volume:
10
Issue:
4
Publication Date:
April 28, 2015
Pagination:
e0125151

Abstract

BACKGROUND:

African Americans (AAs) have lower circulating 25-hydroxyvitamin D3 [25(OH)D3] concentrations and higher prostate cancer (CaP) aggressiveness than other racial/ethnic groups. The purpose of the current study was to examine the relationship between plasma 25(OH)D3, African ancestry and CaP aggressiveness among AAs and European Americans (EAs).

METHODS:

Plasma 25(OH)D3 was measured using LC-MS/MS (Liquid Chromatography Tandem Mass Spectrometry) in 537 AA and 663 EA newly-diagnosed CaP patients from the North Carolina-Louisiana Prostate Cancer Project (PCaP) classified as having either 'high' or 'low' aggressive disease based on clinical stage, Gleason grade and prostate specific antigen at diagnosis. Mean plasma 25(OH)D3 concentrations were compared by proportion of African ancestry. Logistic regression was used to calculate multivariable adjusted odds ratios (OR) and 95% confidence intervals (95%CI) for high aggressive CaP by tertile of plasma 25(OH)D3.

RESULTS:

AAs with highest percent African ancestry (>95%) had the lowest mean plasma 25(OH)D3 concentrations. Overall, plasma 25(OH)D3 was associated positively with aggressiveness among AA men, an association that was modified by calcium intake (ORT 3vs.T1: 2.23, 95%CI: 1.26-3.95 among men with low calcium intake, and ORT 3vs.T1: 0.19, 95%CI: 0.05-0.70 among men with high calcium intake). Among EAs, the point estimates of the ORs were <1.0 for the upper tertiles with CIs that included the null.

CONCLUSIONS:

Among AAs, plasma 25(OH)D3 was associated positively with CaP aggressiveness among men with low calcium intake and inversely among men with high calcium intake. The clinical significance of circulating concentrations of 25(OH)D3 and interactions with calcium intake in the AA population warrants further study.
Show Abstract

Thioredoxin 1 in Prostate Tissue Is Associated with Gleason Score, Erythrocyte Antioxidant Enzyme Activity, and Dietary Antioxidants.
Publication Type:
Article
Year of Publication:
2015
Author(s):
Vance TM, Azabdaftari G, Pop EA, Lee SG, Su LJ, Fontham ET, Bensen JT, Steck SE, Arab L, Mohler JL, Chen MH, Koo SI, Chun OK. Prostate Cancer. 2015; 2015:728046. doi: 10.1155/2015/728046. Epub 2015 Aug 18. PubMed PMID: 26357575; PubMed Central PMCID: PMC4556330.
Source:
Prostate Cancer
Volume:

Issue:

Publication Date:
Aug 18, 2015
Pagination:

Abstract

Background. Prostate cancer is the most common noncutaneous cancer and second leading cause of cancer-related mortality in men in the US. Growing evidence suggests that oxidative stress is involved in prostate cancer. Methods. In this study, thioredoxin 1 (Trx 1), an enzyme and subcellular indicator of redox status, was measured in prostate biopsy tissue from 55 men from the North Carolina-Louisiana Prostate Cancer Project. A pathologist blindly scored levels of Trx 1. The association between Trx 1 and the Gleason score, erythrocyte antioxidant enzyme activity, and dietary antioxidant intake was determined using Fisher's exact test. Results. Trx 1 levels in benign prostate tissue in men with incident prostate cancer were positively associated with the Gleason score (P = 0.01) and inversely associated with dietary antioxidant intake (P = 0.03). In prostate cancer tissue, Trx 1 levels were associated with erythrocyte glutathione peroxidase activity (P = 0.01). No association was found for other erythrocyte enzymes. Greater Gleason score of malignant tissue corresponds to a greater difference in Trx 1 levels between malignant and benign tissue (P = 0.04). Conclusion. These results suggest that the redox status of prostate tissue is associated with prostate cancer grade and both endogenous and exogenous antioxidants.
Show Abstract

Associations between patient-provider communication and socio-cultural factors in prostate cancer patients: a cross-sectional evaluation of racial differences.
Publication Type:
Article
Year of Publication:
2014
Author(s):
Song L, Weaver MA, Chen RC, Bensen JT, Fontham E, Mohler JL, Mishel M, Godley PA, Sleath B.
Source:
Patient Educ Couns.
Volume:
97
Issue:
3
Publication Date:
Dec 2014
Pagination:
339-46

Abstract

OBJECTIVE:

To examine the association between socio-cultural factors and patient-provider communication and related racial differences.

METHODS:

Data analysis included 1854 men with prostate cancer from a population-based study. Participants completed an assessment of communication variables, physician trust, perceived racism, religious beliefs, traditional health beliefs, and health literacy. A multi-group structural equation modeling approach was used to address the research aims.

RESULTS:

Compared with African Americans, Caucasian Americans had significantly greater mean scores of interpersonal treatment (p<0.01), prostate cancer communication (p<0.001), and physician trust (p<0.001), but lower mean scores of religious beliefs, traditional health beliefs, and perceived racism (all p values <0.001). For both African and Caucasian Americans, better patient-provider communication was associated with more physician trust, less perceived racism, greater religious beliefs (all p-values <0.01), and at least high school education (p<0.05).

CONCLUSION:

Socio-cultural factors are associated with patient-provider communication among men with cancer. No evidence supported associations differed by race.

PRACTICE IMPLICATION:

To facilitate patient-provider communication during prostate cancer care, providers need to be aware of patient education levels, engage in behaviors that enhance trust, treat patients equally, respect religious beliefs, and reduce the difficulty level of the information.


KEYWORDS:

Beliefs; Communication; Literacy; PCaP; Physician trust; Prostate cancer; Race; Racism
Show Abstract

Androgenic biomarker profiling in human matrices and cell culture samples using high throughput, electrospray tandem mass spectrometry.
Publication Type:
Article
Year of Publication:
2014
Author(s):
Wilton JH, Titus MA, Efstathiou E, Fetterly GJ, Mohler JL.
Source:
Prostate
Volume:
74
Issue:
7
Publication Date:
May 2014
Pagination:
722-31

Abstract

BACKGROUND. A high throughput, high pressure liquid chromatographic (HPLC) method with triple quadrupole mass spectral detection (LC/MS/MS) was validated for the measurement of 5 endogenous androgens in human plasma and serum and applied to various in vivo and in vitro study samples to pursue a better understanding of the interrelationship of the androgen axis, intracrine metabolism, and castration-recurrent prostate cancer (CaP).

METHODS:

A Shimadzu HPLC system interfaced with a Sciex QTRAP 5500 mass spectrometer with electrospray ionization was used with in line column-switching. Samples were liquid/liquid extracted and chromatographed on a Luna C18(2) column at 60°C with a biphasic gradient using a 15-min run time.

RESULTS:

The method was validated for five androgens in human plasma and serum, and applied to four sets of samples. Plasma (n=188) and bone marrow aspirate (n=129) samples from patients with CaP, who received abiraterone acetate plus prednisone for up to 945 days(135 weeks), had undetectable androgens after 8 weeks of treatment. Plasma dehydroepiandrosterone(DHEA) concentrations were higher in African Americans than Caucasian Americans with newly diagnosed CaP. Analysis of prostate tumor tissue homogenates demonstrated reproducible testosterone (T) and dihydrotestosterone (DHT) concentrations with a minimal sample size of 1.0–2.0 mg of tissue. Finally, cell pellet and media samples from the LNCaP C4-2 cell line showed conversion of T to DHT.

CONCLUSION:

The proposed LC/MS/MS method was validated for quantitation of five endogenous androgens in human plasma and serum, and effectively profiles androgens in clinical specimens and cell culture samples.
Show Abstract

Dietary antioxidants and prostate cancer: a review.
Publication Type:
Article
Year of Publication:
2013
Author(s):
Vance TM, Su J, Fontham ET, Koo SI, Chun OK.
Source:
Nutr Cancer
Volume:
65
Issue:
6
Publication Date:
2013
Pagination:
793-801

Abstract

Prostate cancer is the most common noncutaneous cancer in men in the United States. Several studies have examined the relationship between prostate cancer and antioxidants; however, the results of these studies are inconsistent. This article provides a systematic review of studies on prostate cancer and antioxidant intake from diet and supplements. Tea and coffee appear to offer protection against advanced prostate cancer. Different forms of vitamin E appear to exert different effects on prostate cancer, with alpha-tocopherol potentially increasing and gamma-tocopherol potentially decreasing risk of the disease. There is no strong evidence for a beneficial effect of selenium, vitamin C, or beta-carotene, whereas lycopene appears to be negatively associated with risk of the disease. The effect of dietary antioxidants on prostate cancer remains undefined and inconclusive, with different antioxidants affecting prostate cancer risk differentially. Further studies are needed to clarify the relationship between antioxidants and prostate cancer risk and to delineate the underlying mechanisms.
Show Abstract

Admixture mapping of prostate cancer in African Americans participating in the North Carolina-Louisiana Prostate Cancer Project (PCaP).
Publication Type:
Article
Year of Publication:
2014
Author(s):
Bensen JT, Xu Z, McKeique PM, Smith GL, Mohler JL, Taylor JA.
Source:
Prostate
Volume:
74
Issue:
1
Publication Date:
Jan 2014
Pagination:
1-9

Abstract

BACKGROUND:

Few genetic risk factors have been uncovered that contribute specifically to the racial disparity in prostate cancer (CaP) observed in African Americans (AA). With the advent of ancestry informative marker (AIM) single nucleotide polymorphism (SNP) panels and powerful genetic strategies such as mapping by admixture linkage disequilibrium (MALD) it is possible to discover genes that underlie ethnic variation in disease risk.

METHODS:

One thousand one hundred thirty AA CaP cases enrolled in the North Carolina-Louisiana Prostate Cancer Project (PCaP) were genotyped using a 1,509 AIM SNP panel. MALD was performed using ADMIXMAP to test for linkage between CaP risk and ancestry estimates at each AIM SNP.

RESULTS:

The largest increase of African ancestry was observed at marker rs12543473 (P = 0.0011), located on chromosome 8q24.21, and the greatest excess of European ancestry was observed at marker rs10768140 (P = 0.0004) at chromosome 11p13.

CONCLUSIONS:

The study confirmed the 8q24 risk loci and identified a novel genomic region on 11p13 that is associated with CaP risk. These findings should be replicated in larger AA populations and combined with fine mapping data to further refine the novel 11p13 CaP risk loci.
Show Abstract

Receipt of National Comprehensive Cancer Network guideline-concordant prostate cancer care among African American and Caucasian American men in North Carolina.
Publication Type:
Article
Year of Publication:
2013
Author(s):
Ellis S, Blackard B, Carpenter W, Schroeder J, Mishel M, Chen R, Godley P, Mohler J, Bensen JT
Source:
Cancer
Volume:
119
Issue:
2
Publication Date:
June 15, 2013
Pagination:
2282-90

Abstract

BACKGROUND:

African Americans have a higher incidence of prostate cancer and experience poorer outcomes compared with Caucasian Americans. Racial differences in care are well documented; however, few studies have characterized patients based on their prostate cancer risk category, which is required to differentiate appropriate from inappropriate guideline application.

METHODS:

The medical records of a population-based sample of 777 North Carolina men with newly diagnosed prostate cancer were studied to assess the association among patient race, clinical factors, and National Comprehensive Cancer Network (NCCN) guideline-concordant prostate cancer care.

RESULTS:

African Americans presented with significantly higher Gleason scores (P = .025) and prostate-specific antigen levels (P = .008) than did Caucasian Americans. However, when clinical T stage was considered as well, difference in overall risk category only approached statistical significance (P = .055). Across risk categories, African Americans were less likely to have surgery (58.1% versus 68.0%, P = .004) and more likely to have radiation (39.0% versus 27.4%, P = .001) compared with Caucasian Americans. However, 83.5% of men received guideline-concordant care within 1 year of diagnosis, which did not differ by race in multivariable analysis (odds ratio = 0.83; 95% confidence interval  = 0.54-1.25). Greater patient-perceived access to care was associated with greater odds of receiving guideline-concordant care (odds ratio = 1.06; 95% confidence interval = 1.01-1.12).

CONCLUSIONS:

After controlling for NCCN risk category, there were no racial differences in receipt of guideline-concordant care. Efforts to improve prostate cancer treatment outcomes should focus on improving access to the health care system.
Show Abstract

Patient-health care provider communication among patients with newly diagnosed prostate cancer: Findings from a population-based study.
Publication Type:
Article
Year of Publication:
2013
Author(s):
Song L, Bensen JT , Zimmer C, Sleath B, Blackard B, Fontham E, Su LJ, Brennan CS, Mohler JL, Mishel M.
Source:
Patient Education and Counseling
Volume:
91
Issue:
1
Publication Date:
April 2013
Pagination:
79-84

Abstract

OBJECTIVE:

To examine the multidimensional concept of patient-health care provider (HCP) communication, its effects on patient satisfaction with oncology care services, and related racial differences.

METHODS:

The current analysis draws from a population-based survey sample of 1011 African American and 1034 Caucasian American men with newly diagnosed prostate cancer. The variables of satisfaction with health care services, interpersonal treatment, contextual knowledge of the patient, and prostate cancer communication were analyzed using multiple-group structural equation modeling.

RESULTS:

Regardless of race, patient-HCP communication was related positively to interpersonal treatment by the HCP, HCP's contextual knowledge of the patient, and prostate cancer communication. More positive patient-HCP communication was related to more satisfaction with health care services. Racial differences were significant in the relationships between patient-HCP communication and prostate cancer communication.

CONCLUSION:

Content and interpersonal relationships are important aspects of patient-HCP communication and affect patient satisfaction with oncologic care for prostate cancer.

PRACTICE IMPLICATIONS:

HCPs need to integrate the transfer of information with emotional support and interpersonal connection when they communicate with men with newly diagnosed prostate cancer.
Show Abstract

The influence of mistrust, racism, religious participation, and access to care on patient satisfaction for African-American men: The North Carolina-Louisiana Prostate Cancer Project (PCaP).
Publication Type:
Article
Year of Publication:
2013
Author(s):
Moore AD, Knafl GJ, Hamilton JB, Godley PA, Carpenter WR, Bensen JT , Mohler JL, Mishel M.
Source:
Journal of the National Medical Association
Volume:
105
Issue:
1
Publication Date:
2013
Pagination:
59-68

Abstract

OBJECTIVE:

The purpose of this study was to explore whether a particular combination of individual characteristics influences patient satisfaction with the health care system among a sample of African American men in North Carolina with prostate cancer. Patient satisfaction may be relevant for improving African American men's use of regular care, thus improving the early detection of prostate cancer and attenuating racial disparities in prostate cancer outcomes.

METHODS:

This descriptive correlation study examined relationships of individual characteristics that influence patient satisfaction using data from 505 African American men from North Carolina, who prospectively enrolled in the North Carolina-Louisiana Prostate Cancer Project from September 2004 to November 2007. Analyses consisted of univariate statistics, bivariate analysis, and multiple regression analysis.

RESULTS:

The variables selected for the final model were: participation in religious activities, mistrust, racism, and perceived access to care. In this study, both cultural variables, mistrust (p=<.0001, F=95.58) and racism (p=<.002, F=5.59), were significantly negatively associated with patient satisfaction and accounted for the majority of the variability represented by individual characteristics.

CONCLUSION:

Mistrust and racism are cultural factors that are extremely important and have been negatively associated with patient satisfaction and decreased desires to utilize health care services for African American men. To overcome barriers in seeking health care services, health care providers need to implement a patient-centered approach by creating a clinical environment that demonstrates cultural competence and eliminating policies, procedures, processes, or personnel that foster mistrust and racism.
Show Abstract

Who makes the decision regarding the treatment of clinically localized prostate cancer-the patient or physician? Results from a population-based study.
Publication Type:
Article
Year of Publication:
2013
Author(s):
Song L, Chen RC, Bensen JT , Knafl GJ, Nielsen ME, Farnan L, Wallen EM, Mishel M, Pruthi RS, Mohler JL, Godley PA.
Source:
Cancer
Volume:
119
Issue:
2
Publication Date:
Jan 15 2013
Pagination:
421-8

Abstract

BACKGROUND:

The current study examined how patients' sociodemographic, cancer-related, and subjective affective factors impacted their role in treatment decision-making.

METHODS:

The patient sample (N = 788) was taken from a prospective follow-up study of a population-based cohort. Participants included 343 African American and 445 Caucasian-American patients with clinically localized prostate cancer. Multinomial logistic regression was used to investigate relations between the explanatory variables and the nominal 3-level decision-making variable: patient-only, patient-physician shared, and physician-only.

RESULTS:

Approximately 41% of patients reported patient-only decision-making, 45% reported shared decision-making, and 13% reported physician-only decision-making. The odds of patient-only over physician-only decision-making were greater for younger men (vs those aged ≥ 65 years) (odds ratio [OR], 1.68; 95% confidence interval [95% CI], 1.03-2.74), and were less for men with high (vs low) cancer aggressiveness (OR,0.29; 95% CI, 0.15-0.55). The odds of shared over physician-only decision-making were less for men with high (vs low) cancer aggressiveness (OR, 0.40; 95% CI, 0.22-0.73). Greater odds of patient-only and shared decision-making also were found to be associated with greater concerns about the physical impact of treatment and having enough time for decision-making and lower scores of receiving advice from others.

CONCLUSIONS:

The findings of the current study indicate that, to facilitate a more patient-oriented decision-making process regarding treatment in those with clinically localized prostate cancer, clinicians need to tailor their interventions according to patient age and cancer aggressiveness, help reduce patient concerns and misconceptions regarding the physical impact of treatments, allow sufficient time for patients to consider treatment options, and assist patients in balancing advice and information received from different sources.
Show Abstract

The association between calcium channel blocker use and prostate cancer outcome.
Publication Type:
Article
Year of Publication:
2012
Author(s):
Poch MA, Mehedint D, Curtis A, Green DJ, Payne-Ondracek R, Fontham ETH, Bensen J , Attwood K, Wilding GE, Guru KA, Underwood W, Mohler JL, Heemers HV.
Source:
The Prostate
Volume:
73
Issue:
8
Publication Date:
Dec 31 2012
Pagination:
865-72

Abstract

BACKGROUND:

Epidemiological studies indicate that calcium channel blocker (CCB) use is inversely related to prostate cancer (PCa) incidence. The association between CCB use and PCa aggressiveness at the time of radical prostatectomy (RP) and outcome after RP was examined.

METHODS:

Medication use, PCa aggressiveness and post-RP outcome were retrieved from a prospectively populated database that contains clinical and outcome for RP patients at Roswell Park Cancer Institute (RPCI) from 1993 to 2010. The database was queried for anti-hypertensive medication use at diagnosis for patients with ≥1 year follow-up. Recurrence was defined using NCCN guidelines. Chi-Square tests assessed the relationship between CCB use and PCa aggressiveness. Cox regression models compared the distribution of progression-free survival (PFS) and overall survival (OS) with adjustment for covariates. Results for association between CCB usage and PCa aggressiveness were validated using data from the population-based North Carolina-Louisiana Prostate Cancer Project (PCaP).

RESULTS:

48%, 37%, and 15% of RPCI's RP patients (n = 875) had low, intermediate, and high aggressive PCa, respectively. 104 (11%) had a history of CCB use. Patients taking CCBs were more likely to be older, have a higher BMI and use additional anti-hypertensive medications. Diagnostic PSA levels, PCa aggressiveness, and margin status were similar for CCB users and non-users. PFS and OS did not differ between the two groups. Tumor aggressiveness was associated with PFS. CCB use in the PCaP study population was not associated with PCa aggressiveness.

CONCLUSIONS:

CCB use is not associated with PCa aggressiveness at diagnosis, PFS or OS.
Show Abstract

Intake of grains and fiber and prostate cancer aggressiveness by race.
Publication Type:
Article
Year of Publication:
2012
Author(s):
Tabung F, Steck SE, Su LJ, Mohler JL, Fontham ETH, Bensen JT , Hebert JR, Zhang H, Arab L.
Source:
Prostate Cancer
Volume:

Issue:

Publication Date:
Nov 13 2012
Pagination:

Abstract

Purpose. To examine the associations among intake of refined grains, whole grains and dietary fiber and aggressiveness of prostate cancer in African Americans (AA, n = 930) and European Americans (EA, n = 993) in a population-based, case-only study (The North Carolina-Louisiana Prostate Cancer Project, PCaP). Methods. Prostate cancer aggressiveness was categorized as high, intermediate or low based on Gleason grade, PSA level and clinical stage. Dietary intake was assessed utilizing the NCI Diet History Questionnaire. Logistic regression (comparing high to intermediate/low aggressive cancers) and polytomous regression with adjustment for potential confounders were used to determine odds of high prostate cancer aggressiveness with intake of refined grains, whole grains and dietary fiber from all sources. Results. An inverse association with aggressive prostate cancer was observed in the 2nd and 3rd tertiles of total fiber intake (OR = 0.70; 95% CI, 0.50-0.97 and OR = 0.61; 95% CI, 0.40-0.93, resp.) as compared to the lowest tertile of intake. In the race-stratified analyses, inverse associations were observed in the 3rd tertile of total fiber intake for EA (OR = 0.44; 95% CI, 0.23-0.87) and the 2nd tertile of intake for AA (OR = 0.57; 95% CI, 0.35-0.95). Conclusions. Dietary fiber intake was inversely associated with aggressive prostate cancer among both AA and EA men.
Show Abstract

Patient satisfaction influenced by interpersonal treatment and communication for African-American men: The North Carolina-Louisiana Prostate Cancer Project (PCaP).
Publication Type:
Article
Year of Publication:

Author(s):
Moore AD, Mishel M, Knafl GJ, Hamilton JB, Godley PA, Carpenter WR, Bensen JT.
Source:
American Journal of Men's Health
Volume:
6
Issue:
5
Publication Date:
Sep 2012
Pagination:
409-419

Abstract

The purpose of this study was to determine if a particular set of health behaviors of health care providers and African American men (AAM) influence patient satisfaction from the AAM's perspective. This descriptive, correlational study consisted of 505 AAM in North Carolina diagnosed with prostate cancer and enrolled in the North Carolina-Louisiana Prostate Cancer Project (PCaP). Analyses consisted of bivariate analyses and multiple regression. Patient-to-provider communication, interpersonal treatment, and provider-to-patient communication accounted for 45% (p ≤ .0001) of the variability in patient satisfaction. Interpersonal treatment (provider focusing on the patient) explained the greatest amount (F = 313.53, R² = .39) of patient satisfaction. Since interpersonal treatment focuses on the patient and demonstrated to be the strongest predictor in patient satisfaction, it is noteworthy to consider the emphasis that should be placed on patient-centered care. In addition, knowing important variables positively affecting patient satisfaction provides useful information for developing appropriate interventions to improve AAM health care experiences.
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The differences in quality of life in Prostate Cancer Project: Methods and design of a multidisciplinary population-based follow-up study.
Publication Type:
Article
Year of Publication:
2012
Author(s):
Brennan C, Oral E, Fontham E, Mohler JL, Bensen JT , Mishel M, Simonsen N.
Source:
Americna Medical Journal
Volume:
3
Issue:
2
Publication Date:
2012
Pagination:
104-114

Abstract

Problem statement: Numerous studies have examined the Health Related Quality of Life (HRQoL) in Prostate Cancer (PCa) survivors but few have examined potential differences between races. The causes for alterations in HRQoL in PCa survivors have not been thoroughly explored either, limiting insight regarding potential means to improve their quality of life. Using a large sample of approximately equal numbers of Caucasian-American (CA) and African-American (AA) PCa survivors, the Quality of Life in Prostate Cancer Project (Q-PCaP) is designed to determine if there is a disparity in HRQoL between these groups. Furthermore, QPCaP will determine to what extent certain factors, specifically Healthy Life Behaviors (HLBs), socioeconomic determinants and cultural characteristics of AA and CA PCa survivors affect HRQoL and provide an explanation for any potential disparities observed. Approach: Q-PCaP is a follow-up study built upon a population-based study, the North Carolina-Louisiana Prostate Cancer Project (PCaP). PCaP enrolled men with newly-diagnosed PCa from specific regions of these two states from September 2004 through August 2009. Q-PCaP is designed to collect follow up HRQoL data from the Louisiana cohort of PCaP 3-6 years after their initial baseline interview. Subjects’ current HLBs, social, economical, physical and emotional status, including prostate-related symptoms and other comorbidities, as well as their self-reported experience regarding PCa treatment and health care, will be collected via telephone interviews. The presence and degree of any disparity in the HRQoL between AA and CA PCa survivors will be evaluated. Results: The study will generate a rich archive of follow-up data for a well-characterized population-based cohort of men with PCa to improve understanding of the determinants and disparities in HRQoL. Primary data collection activities are expected to continue through January 2013, yielding approximately 900 enrolled PCa survivors. Conclusion: HLBs are potentially modifiable factors affecting the HRQoL of PCa survivorship. Identifying those that contribute the most to HRQoL and instituting interventions to alter “unhealthy” behaviors may make it possible to not only improve overall HRQoL of PCa survivors, but to reduce racial disparities.
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Coffee consumption and prostate cancer aggressiveness among African and Caucasian Americans in a population-based study.
Publication Type:
Article
Year of Publication:
2012
Author(s):
Arab L, Su LJ, Steck SE, Ang A, Fontham ETH, Bensen JT , Mohler JL.
Source:
Nutrition and Cancer
Volume:
64
Issue:
5
Publication Date:
2012
Pagination:
637-42

Abstract

This study evaluated the relationship between caffeinated and decaffeinated coffee and prostate cancer (CaP) aggressiveness using data from a population-based incident CaP study within the North Carolina-Louisiana Prostate Cancer Project (PCaP). Classification of CaP aggressiveness at diagnosis was based on clinical criteria for 1,049 African-American (AA) and 1,083 Caucasian-American (CA) research subjects. Coffee consumption was measured using a modified NCI Dietary History Questionnaire. No significant associations were found between CaP aggressiveness and consumption of either caffeinated or decaffeinated coffee. The OR for high aggressive CaP among consumers of more than 4 cups per day was 0.92 (95%CI = 0.61, 1.39), compared to non-coffee-drinkers. Results stratified by race found no significant associations and no noticeable trends in either AAs (P for trend = 0. 62) or CAs (P for trend = 0.42). In contrast to a recent report on a select population that has less complete information on CaP aggressiveness suggesting that coffee prevents aggressive CaP, this rapid case ascertainment population-based study, in a biracial population with differing risks of CaP did not demonstrate a protective relationship between high coffee consumption and risk of high aggressive CaP.
Show Abstract

Genetic polymorphism and prostate cancer aggressiveness: a case-only study of 1,536 GWAS and candidate SNPs in African-Americans and European-Americans.
Publication Type:
Article
Year of Publication:
2013
Author(s):
Bensen JT, Xu Z, Smith GJ, Mohler JL, Fontham ET, Taylor JA.
Source:
Prostate
Volume:
73
Issue:
1
Publication Date:
Jan 2013
Pagination:
11-22

Abstract

BACKGROUND:

Genome-wide association studies have established a number of replicated single nucleotide polymorphisms (SNPs) for susceptibility to prostate cancer (CaP), but it is unclear whether these susceptibility SNPs are also associated with disease aggressiveness. This study evaluates whether such replication SNPs or other candidate SNPs are associated with CaP aggressiveness in African-American (AA) and European-American (EA) men.

METHODS:

A 1,536 SNP panel which included 34 genome-wide association study (GWAS) replication SNPs, 38 flanking SNPs, a set of ancestry informative markers, and SNPs in candidate genes and other areas was genotyped in 1,060 AA and 1,087 EA men with incident CaP from the North Carolina-Louisiana Prostate Cancer Project (PCaP). Tests for association were conducted using ordinal logistic regression with a log-additive genotype model and a 3-category CaP aggressiveness variable.

RESULTS:

Four GWAS replication SNPs (rs2660753, rs13254738, rs10090154, rs2735839) and seven flanking SNPs were associated with CaP aggressiveness (P < 0.05) in three genomic regions: One at 3p12 (EA), seven at 8q24 (5 AA, 2 EA), and three at 19q13 at the kallilkrein-related peptidase 3 (KLK3) locus (two AA, one AA and EA). The KLK3 SNPs also were associated with serum prostate-specific antigen (PSA) levels in AA (P < 0.001) but not in EA. A number of the other SNPs showed some evidence of association but none met study-wide significance levels after adjusting for multiple comparisons.

CONCLUSIONS:

Some replicated GWAS susceptibility SNPs may play a role in CaP aggressiveness. However, like susceptibility, these associations are not consistent between racial groups.
Show Abstract

Genetic ancestry, self-reported race and ethnicity in Blacks and Whites in the PCaP cohort.
Publication Type:
Article
Year of Publication:
2012
Author(s):
Sucheston LE, Bensen JT , Xu Z, Singh PK, Mohler JL, Su LJ, Schroeder JC, Fontham ETH, Ruiz B, Smith GJ, Taylor JA.
Source:
PLoS One
Volume:
7
Issue:
3
Publication Date:
Mar 27 2012
Pagination:
e30950

Abstract

BACKGROUND:

Family history and African-American race are important risk factors for both prostate cancer (CaP) incidence and aggressiveness. When studying complex diseases such as CaP that have a heritable component, chances of finding true disease susceptibility alleles can be increased by accounting for genetic ancestry within the population investigated. Race, ethnicity and ancestry were studied in a geographically diverse cohort of men with newly diagnosed CaP.

METHODS:

Individual ancestry (IA) was estimated in the population-based North Carolina and Louisiana Prostate Cancer Project (PCaP), a cohort of 2,106 incident CaP cases (2063 with complete ethnicity information) comprising roughly equal numbers of research subjects reporting as Black/African American (AA) or European American/Caucasian/Caucasian American/White (EA) from North Carolina or Louisiana. Mean genome wide individual ancestry estimates of percent African, European and Asian were obtained and tested for differences by state and ethnicity (Cajun and/or Creole and Hispanic/Latino) using multivariate analysis of variance models. Principal components (PC) were compared to assess differences in genetic composition by self-reported race and ethnicity between and within states.

RESULTS:

Mean individual ancestries differed by state for self-reporting AA (p = 0.03) and EA (p = 0.001). This geographic difference attenuated for AAs who answered "no" to all ethnicity membership questions (non-ethnic research subjects; p = 0.78) but not EA research subjects, p = 0.002. Mean ancestry estimates of self-identified AA Louisiana research subjects for each ethnic group; Cajun only, Creole only and both Cajun and Creole differed significantly from self-identified non-ethnic AA Louisiana research subjects. These ethnicity differences were not seen in those who self-identified as EA.

CONCLUSIONS:

Mean IA differed by race between states, elucidating a potential contributing factor to these differences in AA research participants: self-reported ethnicity. Accurately accounting for genetic admixture in this cohort is essential for future analyses of the genetic and environmental contributions to CaP.
Show Abstract

How does health literacy affect quality of life among men with newly diagnosed clinically localized prostate cancer? Findings from the North Carolina-Louisiana Prostate Cancer Project (PCaP).
Publication Type:
Article
Year of Publication:
2012
Author(s):
Song L, Mishel M, Bensen JT , Chen RC, Knafl GJ, Blackard B, Farnan L, Fontham E, Su LJ, Brennan CS, Mohler JL, Godley PA.
Source:
Cancer
Volume:
118
Issue:
15
Publication Date:
Aug 1 2012
Pagination:
3842-51

Abstract

BACKGROUND:

Health literacy deficits affect half of the US overall patient population, especially the elderly, and are linked to poor health outcomes among noncancer patients. Yet little is known about how health literacy affects cancer populations. The authors examined the relation between health-related quality of life (HRQOL) and health literacy among men with prostate cancer.

METHODS:

Data analysis included 1581 men with newly diagnosed clinically localized prostate cancer from a population-based study, the North Carolina-Louisiana Prostate Cancer Project (PCaP). Participants completed assessment of health literacy using Rapid Estimate of Adult Literacy in Medicine (REALM) and HRQOL using the Short Form-12 General Health Survey (SF12). Bivariate and multivariate regression was used to determine the potential association between REALM and HRQOL, while controlling for sociodemographic and illness-related variables.

RESULTS:

Higher health literacy level was significantly associated with better mental well-being (SF12-Mental Component Summary [MCS]; P < .001) and physical well-being (SF12-Physical Component Summary [PCS]; P < .001) in bivariate analyses. After controlling for sociodemographic (age, marital status, race, income, and education) and illness-related factors (types of cancer treatment, tumor aggressiveness, and comorbidities), health literacy remained significantly associated with SF12-MCS scores (P < .05) but not with SF12-PCS scores.

CONCLUSIONS:

Among patients with newly diagnosed localized prostate cancer, those with low health literacy levels were more vulnerable to mental distress than those with higher health literacy levels, but physical well-being was no different. These findings suggest that health literacy may be important in patients managing prostate cancer and the effects of treatment, and provide the hypothesis that supportive interventions targeting patients with lower health literacy may improve their HRQOL.
Show Abstract

Obesity and prostate cancer aggressiveness among African and Caucasian Americans in a population-based study.
Publication Type:
Article
Year of Publication:
2011
Author(s):
Su LJ, Arab L, Steck SE, Fontham ETH, Schroeder JC, Bensen JT , Mohler JL.
Source:
Cancer Epidemiol Biomarkers Prev.
Volume:
20
Issue:
5
Publication Date:
May 2011
Pagination:
844-853

Abstract

BACKGROUND:

This study evaluated obesity and prostate cancer aggressiveness relationship in a population-based incident prostate cancer study.

METHODS:

The North Carolina-Louisiana Prostate Cancer Project includes medical records data for classification of prostate cancer aggressiveness at diagnosis by using clinical criteria for 1,049 African American (AA) and 1,083 Caucasian American (CA) participants. An association between prostate cancer aggressiveness and obesity, measured using body mass indices (BMI) and waist-to-hip ratio (WHR), was assessed using ORs and 95% CIs adjusted for confounders.

RESULTS:

A significantly positive association was found between prostate cancer aggressiveness and obesity. The ORs for high aggressive prostate cancer among prediagnosis obese and severely obese were 1.48 (95% CI = 1.02-2.16) and 1.98 (95% CI = 1.31-2.97), respectively, compared with normal weight research subjects. Race-stratified results suggested the association is stronger among CAs. Interaction model showed that normal weight AAs had more aggressive prostate cancer than normal weight CAs (OR = 2.69, 95% CI = 1.36-5.30); severe obesity was associated with aggressive disease in AAs (OR = 3.90, 95% CI = 1.97-7.75). WHR > 0.98 among all research subjects adjusted for race was significantly associated with high aggressive prostate cancer (OR = 1.42, 95% CI = 1.00-2.00) when compared with WHR < 0.90. The stratified result is less clear among AAs.

CONCLUSIONS:

This study shows a positive association between obesity and aggressive prostate cancer. AAs have more aggressive prostate cancer in general than CAs even at normal weight. Therefore, the association between obesity and aggressiveness is not as evident in AAs as in CAs.

IMPACT:

This study provides a unique opportunity to examine impact of race on obesity and high aggressive prostate cancer relationship.
Show Abstract

GWAS SNP replication among African American and European American men in the North Carolina-Louisiana Prostate Cancer Project (PCaP).
Publication Type:
Article
Year of Publication:
2011
Author(s):
Xu Z*, Bensen JT * (*joint first authors), Smith GJ, Mohler, JL, Taylor JA.
Source:
Prostate
Volume:
71
Issue:
8
Publication Date:
2011
Pagination:
881-891

Abstract

BACKGROUND:

Genome-wide association studies (GWAS) have identified numerous common SNPs associated with prostate cancer (CaP) risk in men of European descent. This study evaluates GWAS SNPs associated with CaP in African Americans (AAs) and European Americans (EA).

METHODS:

Eight hundred SNPs were genotyped, including 32 from European-based GWAS and 35 flanking SNPs, in 417 AA and 455 EA cases from the NC-LA Prostate Cancer Project (PCaP) and compared to 925 AA and 1,687 EA controls from Illumina's iControlDB. The 32 GWAS SNPs were evaluated for their predictive power to discriminate between cases and controls using ROC curves.

RESULTS:

Of the 32 GWAS SNPs, 13 were significant at P < 0.05 in EA and 4 in AA (rs6983267, rs7017300, rs1859962, rs6501455). Three of 35 flanking SNPs, all from chromosome 8q, reached study-wide significance (P < 3.5 × 10(-5)); 2 in AA (rs10505476 rs6985504) and 1 in EA (rs16901970). Among the remaining 656 SNPs, 2 were associated with CaP (P < 3.5 × 10(-5)): rs1472606 (OR: 1.43 in EA) and rs9351265 (OR: 1.48 in AA) both in intergenic regions. For the 32 GWAS SNPs, ROC plots yielded AUC estimates too low for clinical use (EA AUC = 0.60 and AA AUC = 0.56).

CONCLUSIONS:

This study confirms a large proportion of CaP associated regions implicated by European-based GWAS and provides evidence that some regions may be important in AA CaP risk. Despite the identification of a large panel of GWAS replicated SNPs for CaP, this panel is not appropriate for clinical screening.
Show Abstract

Comparison of ACINUS, caspase-3, and TUNEL as apoptotic markers in determination of tumor growth rates of clinically localized prostate cancer using image analysis.
Publication Type:
Article
Year of Publication:
2009
Author(s):
Singh SS, Mehedint DC, Ford OH 3rd, Jeyaraj DA, Pop EA, Maygarden SJ, Ivanova A, Chandrasekhar R, Wilding GE, Mohler JL.
Source:
Prostate
Volume:
69
Issue:
15
Publication Date:
Nov 1 2009
Pagination:
1603-10

Abstract

BACKGROUND:

The balance between apoptotic and proliferative processes determines the enlargement of a tumor. Accurate measurement of apoptotic and proliferative rates from diagnostic prostate biopsies would allow calculation of tumor growth rates in a population-based prostate cancer (CaP) study. Automated image analysis may be used if proliferation and apoptotic biomarkers provide clearly resolved immunostained images.

METHODS:

Clinical CaP aggressiveness was assigned as low, intermediate or high using clinical criteria for 46 research subjects with newly diagnosed CaP. Diagnostic biopsy sections from the research subjects were dual-labeled for proliferation biomarker, Ki-67 and apoptotic biomarker, apoptotic chromatin condensation inducer in the nucleus (ACINUS). Apoptotic biomarkers, caspase-3 and terminal deoxyribonucleotidyltransferase mediated dUTP-biotin nick end labeling (TUNEL) were labeled separately. Images from immunostained sections were analyzed using automated image analysis and tumor growth rates computed. Association between clinical CaP aggressiveness and tumor growth rates was explored.

RESULTS:

Sixteen subjects had high, 17 had intermediate, and 13 had low clinical CaP aggressiveness. Positive immunostaining was localized to the nucleus for Ki-67, ACINUS, and TUNEL. A statistically significant linear trend across clinical CaP aggressiveness categories was found when tumor growth rates were calculated using ACINUS (P = 0.046). Logistic regression and ROC plots generated showed ACINUS (AUC = 0.677, P = 0.048) and caspase-3 (AUC = 0.694, P = 0.038) to be better predictors than TUNEL (AUC = 0.669, P = 0.110).

CONCLUSIONS:

ACINUS met the criteria for automated image analysis and for calculation of apoptotic rate. Tumor growth rates determined using automated image analysis should be evaluated for clinical prediction of CaP aggressiveness, treatment response, recurrence, and mortality.
Show Abstract

Racial differences in trust and regular source of patient care, and implications for prostate cancer screening utilization.
Publication Type:
Article
Year of Publication:
2009
Author(s):
Carpenter WR, Godley PA, Clark JA, Talcott JA, Finnegan T, Mishel M, Bensen J , Rayford W, Su LJ, Fontham ETH, Mohler J.
Source:
Cancer
Volume:
115
Issue:
21
Publication Date:
2009
Pagination:
5048-5059

Abstract

BACKGROUND:

Nonmedical factors may modify the biological risk of prostate cancer (PCa) and contribute to the differential use of early detection; curative care; and, ultimately, greater racial disparities in PCa mortality. In this study, the authors examined patients' usual source of care, continuity of care, and mistrust of physicians and their association with racial differences in PCa screening.

METHODS:

: Study nurses conducted in-home interviews of 1031 African-American men and Caucasian-American men aged > or =50 years in North Carolina and Louisiana within weeks of their PCa diagnosis. Medical records were abstracted, and the data were used to conduct bivariate and multivariate analyses.

RESULTS:

: Compared with African Americans, Caucasian Americans exhibited higher physician trust scores and a greater likelihood of reporting a physician office as their usual source of care, seeing the same physician at regular medical encounters, and historically using any PCa screening. Seeing the same physician for regular care was associated with greater trust and screening use. Men who reported their usual source of care as a physician office, hospital clinic, or Veterans Administration facility were more likely to report prior PCa screening than other men. In multivariate regression analysis, seeing the same provider remained associated with prior screening use, whereas both race and trust lost their association with prior screening.

CONCLUSIONS:

: The current results indicated that systems factors, including those that differ among different sources of care and those associated with the continuity of care, may provide tangible targets to address disparities in the use of PCa early detection, may attenuate racial differences in PCa screening use, and may contribute to reduced racial disparities in PCa mortality. Cancer 2009. Published 2009 by the American Cancer Society.
Show Abstract

Feasibility of constructing tissue microarrays from diagnostic prostate biopsies.
Publication Type:
Article
Year of Publication:
2007
Author(s):
Singh SS, Mehedint DC, Ford OH 3rd, Maygarden SJ, Ruiz B, Mohler JL.
Source:
Prostate
Volume:
1
Issue:
67
Publication Date:
2007
Pagination:
1011-8

Abstract

OBJECTIVES:

The ability to construct prostate tissue microarrays (TMAs) using prostate needle biopsies could allow high throughput molecular profiling to search for prostate cancer prognostic biomarkers.

MATERIALS AND METHODS:

Diagnostic prostate biopsies from 13 patients (diagnosed 1996-2000) were obtained from the University of North Carolina (UNC) to construct one prostate TMA under uniform conditions. A second prostate TMA was attempted using diagnostic prostate biopsies from 45 patients (diagnosed 2004) obtained from the North Carolina-Louisiana Prostate Cancer Project (PCaP).

RESULTS:

Eleven men had sufficient prostate cancer in their diagnostic prostate biopsy blocks to construct a UNC TMA that yielded six-micron sections that provided an average of 76% of cores (maximum 99%) to a depth of 360 microm. Diagnostic prostate biopsy blocks from 35 PCaP research subjects were unsuitable for TMA construction as a result of no remaining prostate cancer in 4, insufficient prostate cancer in 9, and insufficient prostate tissue in 22. The PCaP TMA constructed from 10 men yielded an average of 37%, and a maximum of 45%, of cores when sectioned to a depth of 360 microm.

CONCLUSIONS:

TMAs may be constructed from diagnostic prostate biopsies obtained at an academic center under uniform conditions. However, excessive facing of blocks and the large number of re-cuts ordered by many community pathology laboratories deplete diagnostic prostate biopsy tissue. The experience of a population-based study of men with newly diagnosed prostate cancer in Louisiana and North Carolina suggests that TMAs may not be constructed using diagnostic prostate biopsies from men diagnosed with prostate cancer throughout the United States.
Show Abstract

The North Carolina-Louisiana Prostate Cancer Project (PCaP): methods and design of a multidisciplinary population-based cohort study of racial differences in prostate cancer outcomes.
Publication Type:
Article
Year of Publication:
2006
Author(s):
Schroeder JC*, Bensen JT * (*joint first authors), Su LJ, Mishel M, Ivanova A, Godley P, Smith G, Fontham E, Mohler J.
Source:
Prostate
Volume:
1
Issue:
66
Publication Date:
Aug 1 2006
Pagination:
1162-1176

Abstract

BACKGROUND:

The North Carolina-Louisiana Prostate Cancer Project (PCaP) is a multidisciplinary study of social, individual, and tumor-level causes of racial differences in prostate cancer aggressiveness.

METHODS:

A population-based sample of incident prostate cancer cases from North Carolina and Louisiana will include 1,000 African Americans and 1,000 Caucasian Americans. Study nurses administer structured questionnaires and collect blood, adipose tissue, urine, and toenail samples during an in-home visit. Clinical data are abstracted from medical records, diagnostic biopsies are reviewed and assayed, and tissue microarrays are constructed from prostatectomy samples. Prostate cancer aggressiveness is classified based on PSA, clinical stage, and Gleason grade.

RESULTS:

Preliminary data demonstrate between- and within-group differences in patient characteristics, screening, and treatment by race and state. Participation exceeds 70% in all groups.

CONCLUSIONS:

Preliminary data support the feasibility of this comprehensive study to help determine the focus of public health efforts to reduce racial disparities in prostate cancer mortality.
Show Abstract