Genetic polymorphism and prostate cancer aggressiveness: A case-only study of 1,536 GWAS and candidate SNPs in African-Americans and European-Americans

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

Admixture Mapping of Prostate Cancer in African Americans participating in the North Carolina-Louisiana Prostate Cancer Project (PCaP)

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

Racial Differences in Trust and Regular Source of Patient Care, and Implications for Prostate Cancer Screening Utilization

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

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): Carotenoids and Prostate Cancer Aggressiveness

Associations between carotenoid intake and prostate cancer (CaP) incidence have varied across studies. This may be due to 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

The association between calcium channel blocker use and prostate cancer outcome

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

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)

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), Ptrend-=-0.006; δ-tocopherol, 0.45 (0.21-0.95) Ptrend-=-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), Ptrend-=-0.20; supplemental α-tocopherol, 0.64 (0.31-1.21) Ptrend-=-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

Association among plasma 1,25(OH)2D, ratio of 1,25(OH)2D to 25(OH)D, and prostate cancer aggressiveness

Background: African-American (AA) men tend to present with more aggressive prostate cancer (Gleason score \u3e7) 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)2D] 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)2D and 25-hydroxyvitamin D3 [25(OH)D] were measured using liquid chromatography with tandem mass spectrophotometry. Research subjects were classified into low (Gleason sum \u3c 7, stage T1-T2, and Prostate-specific antigen (PSA) \u3c 9 ng/mL) or high (Gleason sum \u3e 8 or Gleason sum = 7 with 4 + 3, or PSA \u3e 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)2D 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)2D/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)2D/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

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)

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. Prostate 76:1053–1066, 2016. © 2016 Wiley Periodicals, Inc

Calcium, magnesium, and whole-milk intakes and high-Aggressive prostate cancer in the North Carolina-Louisiana Prostate Cancer Project (PCaP)

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) \u3e20 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