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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.

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. Cancer Epidemiol Biomarkers Prev; 20(5); 844–53. ©2011 AACR.

Background: Physical activity (PA) has been implicated in the etiology of prostate cancer (CaP). However, there are considerable inconsistencies in the epidemiological literature. This may be due to failure to examine associations by CaP aggressiveness. While most men will develop CaP if they live long enough, usually the disease is indolent; only aggressive disease is of prognostic relevance. Methods: Associations of occupational and recreational PA in relation to CaP aggressiveness at diagnosis were examined in a large population-based, case-only study of incident CaP among African-American (n = 1,023) and European-American (n = 1,079) men (the North Carolina-Louisiana Prostate Cancer Project, PCaP). Men were classified as highly aggressive cases if Gleason sum => 8 or PSA >20ng/ml or Gleason score => 7 and clinical stage T3-T4 (N = 370, 18%). All others (low and intermediate aggressive cases) were classified as the comparison group. Recreational PA was measured using a validated questionnaire and occupational PA was estimated based on current and longest-held job titles. Metabolic equivalents (MET) were estimated for recreational PA and job titles using the Compendium of Physical Activities. Associations between CaP aggressiveness at diagnosis and PA were assessed using logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CI), adjusting for age, race, body mass index, CaP screening history, smoking status, and energy intake. Additional adjustment for educational status was done for the occupational PA models. Results: Recreational PA, particularly walking for 75-150 minutes/week for exercise was associated with 33% lower odds of high aggressive CaP compared to no walking for exercise (OR= 0.67, 95% CI: 0.46-0.98). MET-hours/week from walking for exercise was inversely related to CaP aggressiveness, though did not reach statistical significance (OR= 0.77, 95% CI: 0.57-1.04, highest vs. lowest tertile; Ptrend = 0.08). PA at current job was associated with 28% lower odds of high aggressive CaP (OR= 0.72, 95% CI: 0.54-0.95, highest MET tertile vs. lowest). Conversely, the highest accumulation of PA at longest-held job (>132 MET-years) was associated with 61% higher odds of presenting with high aggressive CaP compared to 60-90 MET-years (OR=1.61, 95% CI: 1.08-2.40). There was no evidence of interaction between PA and race on the association with aggressive CaP. Conclusions: Walking for exercise and higher PA at current job were associated with reduced odds of high aggressive CaP. The positive association between highest PA at longest-held job and CaP aggressiveness may be influenced by residual confounding by low socioeconomic status, which often correlates with unhealthy lifestyle factors, such as poor diet. Funding: PCaP is carried out as a collaborative study supported by the Department of Defense contract DAMD 17-03-2-0052. Citation Format: Samuel Antwi, Susan E. Steck, L. Joseph Su, Bonny Blackard, Swann Arp-Adams, James R. Hebert, Elizabeth TH Fontham, Jeannette Bensen, James L. Mohler, Lenore Arab. Occupational and recreational physical activity in relation to prostate cancer aggressiveness: The North Carolina-Louisiana Prostate Cancer Project (PCaP). [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr B08. doi:10.1158/1538-7755.DISP13-B08

Background: Multivitamin supplement use has been associated with reduced overall cancer incidence in men in one recent trial, though associations with prostate cancer specifically have been null in the majority of previous studies. Most studies did not include a large sample of participants from different races/ethnicities with which to examine differences in effect by race. Multivitamin supplement use has been shown to differ by race/ethnicity; thus, the aim of the current study was to examine associations between multivitamin supplement use and prostate cancer aggressiveness by race. Methods: Data from a large, case-only study of incident prostate cancer with approximate equal enrollment of African Americans and European Americans [the North Carolina-Louisiana Prostate Cancer Project (PCaP)] were utilized to examine the relationship between multivitamin supplement use and prostate cancer aggressiveness at time of diagnosis. Research subjects were classified as highly aggressive cases (n=350) if Gleason score ≥8, or PSA >20ng/ml, or Gleason score ≥7 AND clinical stage T3-T4; or as the comparison group for all other cases with low or intermediate aggressive disease (n=1,720). Information about multivitamin supplement use including brand and frequency of intake one year prior to prostate cancer diagnosis was obtained from an interviewer-administered questionnaire. Multivitamin supplement use was categorized in two ways: 1) yes or no as reported use more than once per week in the previous year, or 2) by frequency as 0, 1-6, or 7 days/week. Multivariable logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (95%CI) for highly aggressive prostate cancer by multivitamin supplement use for all subjects and stratified by race with adjustment for age, education, prostate specific antigen screening history, smoking, body mass index, and energy intake. Results: Overall, fewer men with highly aggressive prostate cancer took multivitamins one year prior to diagnosis as compared to men with low/intermediate aggressive disease (41 vs. 46%). Percent of multivitamin supplement users among African Americans was lower as compared to European Americans (36 vs. 54%, respectively). Overall, multivitamin supplement use was not associated with prostate cancer aggressiveness after adjustment for potential confounders (OR=0.98; 95%CI: 0.77-1.25 for yes vs. no reported use ≥once per week). In European Americans, a two-fold higher risk of highly aggressive prostate cancer was observed in men who consumed multivitamins one to six days per week compared to non-users (OR=2.08; 95%CI: 1.06-4.09), though there was no association among men who used multivitamins seven days per week (OR=1.13; 95%CI:0.78-1.64). There was no association between frequency of intake and prostate cancer aggressiveness among African Americans (OR=0.91; 95%CI:0.46-1.79 for one to six days per week and OR=0.76; 95%CI:0.51-1.79 for seven days per week compared to non-users). Conclusion: African American men were less likely to report taking multivitamins prior to diagnosis than their European American counterparts. Multivitamin intake was not associated with prostate cancer aggressiveness after adjustment for important confounders, though there was a suggestion of increased risk among European American men regularly using multivitamins less than daily as compared to non-users. Future studies in this population examining specific formulations of multivitamins and individual nutrient supplement use are planned. Funding: PCaP is carried out as a collaborative study supported by the Department of Defense contract DAMD 17-03-2-0052. Citation Format: Daria M. McMahon, Susan E. Steck, L. Joseph Su, Hongmei Zhang, James R. Hebert, Jeannette T. Bensen, Elizabeth T. H. Fontham, James L. Mohler, Lenore Arab. Multivitamin supplement use and prostate cancer aggressiveness by race in the North Carolina-Louisiana Prostate Cancer Project (PCaP). [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr B05. doi:10.1158/1538-7755.DISP13-B05

Introduction: Epidemiologic studies have reported conflicting results when examining the relationship between circulating vitamin D metabolites and risk of advanced prostate cancer. While 25-hydroxy vitamin D [25(OH)D] is used as a measure of vitamin D status, 1,25-dihydroxy vitamin D [1,25(OH)2D] is the biologically active form and its concentration is tightly regulated. We previously reported increased odds of aggressive prostate cancer among African Americans in the highest tertile of plasma 25(OH)D compared to the lowest, and have now examined plasma 1,25(OH)2D and the ratio of 1,25(OH)2D to 25(OH)D in relation to prostate cancer aggressiveness. Methods: Plasma 1,25(OH)2D and 25(OH)D were measured using LC/MS/MS in 435 African-American and 563 European-American men with newly-diagnosed prostate cancer from the North Carolina-Louisiana Prostate Cancer Project (PCaP). Men were classified as highly aggressive cases at time of diagnosis if Gleason sum ≥8, or PSA >20 ng/ml, or Gleason sum ≥7 AND clinical stage = T3-T4, or Gleason sum=7 with a pattern of (4+3). The comparison group (low aggressiveness) included men with Gleason sum Results: Plasma 1,25(OH)2D was not associated with odds of aggressive prostate cancer in either African Americans or European Americans in this study (OR=0.83, 95%CI=0.49, 1.41 and OR=0.67, 95%CI=0.40, 1.11, respectively, for highest tertile compared to lowest tertile). However, higher quartiles (as compared to the lowest quartile) of 1,25(OH)2D:25(OH)D ratio were associated with reduced odds of high aggressive disease among African Americans after adjustment for age, season, education, alcohol intake, smoking status, PSA screening history, physical activity, energy intake, use of non-steroidal anti-inflammatory drugs, study site and body mass index (OR=0.51, 95%CI=0.28, 0.91; OR=0.41, 95%CI=0.22, 0.76, and OR=0.46, 95%CI=0.25, 0.84 for 2nd, 3rd and 4th quartiles, respectively). Inverse associations were also observed for European Americans, but were not statistically significant (OR=0.64, 95%CI=0.35, 1.17 for 4th compared to 1st quartile). Conclusions: The ratio of plasma 1,25(OH)2D to 25(OH)D was inversely associated with prostate cancer aggressiveness among African Americans. Blood samples were collected after diagnosis, thus, it is possible that effects of treatment or extent of disease or associated processes (e.g., weight loss) on plasma vitamin D metabolites may have affected their measurement. Future analyses in PCaP will include examining circulating parathyroid hormone, calcium and phosphorus, as well as genotyping of genes encoding enzymes involved in the vitamin D metabolism and activity, which may help to explain these findings. Citation Format: Susan E. Steck, Anna Woloszynska-Read, Lenore Arab, Daria McMahon, Jeannette Bensen, John S. Adams, Elizabeth T.H. Fontham, James L. Mohler, L. Joseph Su, Hongmei Zhang, Donald Trump, Candace Johnson. Ratio of plasma 1,25(OH)2D to 25(OH)D is inversely associated with aggressive prostate cancer in African Americans in the North Carolina-Louisiana Prostate Cancer Project (PCaP). [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr B07. doi:10.1158/1538-7755.DISP13-B07