Fat quality, not quantity, linked to reduced risk of advanced and lethal prostate cancer in US populations: a large prospective multicenter study.

We previously found that higher total 25-hydroxyvitamin D [25(OH)D] levels were associated with lower risk of lethal prostate cancer. However, the relationships of bioavailable 25(OH)D and vitamin D binding protein (VDBP) with risk of advanced and lethal prostate cancer are unclear. In a prospective case-control study of 156 pairs of advanced prostate cancer cases and controls, we directly measured prediagnostic circulating 25(OH)D and VDBP and calculated bioavailable 25(OH)D using a validated formula. We examined the association of bioavailable 25(OH)D and VDBP levels with risk of advanced and lethal prostate cancer and whether total 25(OH)D levels interacted with VDBP levels to affect the risk. Conditional logistic models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Compared to total 25(OH)D (ptrend = 0.02), bioavailable 25(OH)D levels were not more strongly associated with risk of advanced prostate cancer (ptrend = 0.14). Although VDBP levels were not associated with risk of advanced prostate cancer (ptrend = 0.16), we observed an interaction between total 25(OH)D levels and VDBP levels in relation to risk of advanced prostate cancer (pinteraction = 0.03). Compared to those with total 25(OH)D levels below the median and VDBP levels above the median (at highest risk), men with both levels above the median had a multivariable-adjusted OR of 0.31 (95% CI, 0.15-0.65) for advanced prostate cancer. We observed similar results when we restricted the analyses to 116 lethal prostate cancer cases and their controls. Our data suggest that VDBP levels may modify the association between total 25(OH)D levels and risk of advanced and lethal prostate cancer.

Introduction: Epidemiologic data support an inverse association between statin use and risk of lethal prostate cancer, but contributing mechanisms have not been elucidated. Herein, using data from the Health Professionals Follow-up Study (HPFS), we updated our previous analysis of statins and lethal prostate cancer with a decade of additional follow-up, and incorporated immunohistochemistry (IHC)-based biomarkers and gene expression profiling to identify putative molecular mechanisms contributing to the association. Methods: We included data from 44,076 HPFS participants who were cancer free in 1990, with follow-up through 2012. Participants reported prediagnostic statin use on biennial questionnaires. Statin use was categorized as current vs. never/past use, with current users further categorized as long-term vs. short-term users (≥6 vs. <6 years). To classify prostate cancer molecular subtypes, genetically validated IHC assays for TMPRSS2:ERG fusion and PTEN loss were conducted on tissue microarrays for 891 and 660 cases, respectively. Whole-genome mRNA profiling of tumor and adjacent normal tissue was completed for 237 and 114 cases, respectively, using Affymetrix GeneChip Human Gene 1.0 ST arrays. We used Cox proportional hazards analysis to generate hazard ratios (HR) and 95% confidence intervals (CI) for associations between statin use and risk of overall, advanced (stage T3b or higher at diagnosis, metastatic or fatal), and lethal (metastatic or fatal) prostate cancer, as well as molecular subtypes, adjusted for PSA testing behavior and potential confounders including obesity and smoking. Moreover, we explored gene expression pathways in tumor and adjacent normal prostate tissue of statin users vs. nonusers using gene set enrichment analysis (GSEA). Results: During 22 years of follow-up, 6,144 men were diagnosed with prostate cancer; 1,051 (17%) had advanced disease and 827 (13%) developed lethal prostate cancer. Of cases with molecular subtype available, 48% were ERG-positive and 14% PTEN-null. In multivariable analysis, relative to never/past use, current statin use was inversely associated with risk of advanced (HR 0.84; 95% CI 0.68-1.04) and lethal (HR 0.78; 95% CI 0.68-1.01) prostate cancer. These associations were more pronounced in long-term users, where ≥6 years of prediagnosis statin use was significantly associated with a lower risk of advanced (HR 0.72; 95% CI 0.53-0.97) and lethal prostate cancer (HR 0.64; 95% CI 0.45-0.92), relative to nonuse. Long-term statin use was not associated with overall prostate cancer risk, whether ERG-positive (HR 0.89; 95% CI 0.59-1.35) or ERG-negative (HR 1.06; 95% CI 0.74-1.50). However, relative to nonuse, a longer duration of prediagnosis statin use was associated with reduced risk of PTEN-null cancers (HR 0.42; 95% CI 0.20-0.90), but not PTEN-intact disease (HR 1.18; 95% CI 0.95-1.46; p-heterogeneity=0.01). In GSEA, we identified T cell, B cell, and phosphatidylinositol (PI3K) signaling among the top pathways enriched in tumor-adjacent normal prostate tissue of current statin users, relative to never users. Intriguingly, no gene sets were differentially expressed by statin use in the tumor. Discussion: Our updated findings from the HPFS are consistent with our prior findings and other epidemiologic data supporting a role for statins in lethal prostate cancer prevention. Molecular classification of tumors identified PTEN/PI3K signaling and inflammation/immune activation as two potential mechanisms contributing to this association. Elucidating molecular mechanisms mediating the association between statin use and lower risk of lethal prostate cancer will provide support for a causal effect of statins on lethal prostate cancer risk and could inform statin clinical trials with appropriate intermediate endpoints. Citation Format: Emma H. Allott, Ericka M. Ebot, Amparo G. Gonzalez-Feliciano, Sarah C. Markt, Kathryn M. Wilson, Thomas U. Ahearn, Travis A. Gerke, Mary K. Downer, Konrad H. Stopsack, Jennifer R. Rider, Stephen J. Freedland, Elizabeth A. Platz, Meir J. Stampfer, Edward L. Giovannucci, Christopher J. Sweeney, Stephen P. Finn, Lorelei A. Mucci. Molecular tumor profiling to identify mechanisms linking statin use with lower risk of lethal prostate cancer: Results from the Health Professionals Follow-up Study [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr A015.

Prostate cancer is the most common non-cutaneous cancer and second leading cause of cancer death among men in the U.S. Although ecologic and migrant studies suggest that diet plays a role in the etiology of prostate cancer, few specific nutrients that alter its occurrence have been identified in case-control and cohort studies. Phytoestrogens are a family of bioactive compounds that are abundant in soy products and some other food groups (e.g. legumes and chick peas). Experimental studies revealed that phytoestrogen intake may modulate the risk of prostate cancer due to their structural similarity to 17β-estradiol and the resulting competitive binding to estrogen receptors. Despite biological plausibility, it still remains elusive whether phytoestrogen intake influences prostate cancer risk in human populations. Therefore, the objective of the present study was to investigate the associations between dietary intake of phytoestrogens and the risk of total and advanced prostate cancer among 30,097 participants in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO). A total of 3628 cases of prostate cancer (including 396 advanced cases) have been documented during a median follow up of 11.5 years. Advanced prostate cancer were defined as stage II cancer with a Gleason score of ≥8, or stage III or stage IV cancer. Dietary intake of phytoestrogens was assessed with a validated food frequency questionnaire. Cox proportional hazards regression was performed to estimate hazard ratios (HRs) and 95% confidence intervals (CI) for dietary intake of phytoestrogens in relation to prostate cancer risk. After adjustment for confounders, an increased risk of advanced prostate cancer was found for the higher dietary intake of isoflavones (HR: 1.58; 95% CI: 1.11, 2.24), genistein (HR: 1.42; 95% CI: 1.02, 1.98), daidzein (HR: 1.62; 95% CI: 1.13, 2.32), and glycitein (HR: 1.53; 95% CI: 1.09, 2.15). Conversely, it appears that the higher dietary intake of genistein was associated with a reduced risk of non-advanced prostate cancer (HR: 0.88; 95% CI: 0.78, 0.99) and total prostate cancer (HR: 0.90; 95% CI: 0.81, 1.00). The risk estimates presented above were obtained for comparisons between the quintile 5 and quintile 1 of respective phytoestrogen intake. In summary, our analysis of this national prospective cohort study suggests that dietary intake of phytoestrogens modulated the risk of prostate cancer and that some of these effects may differ by the aggressiveness of the disease. Citation Format: Michael Reger, Terrell Zollinger, Ziyue Liu, Josette Jones, Jianjun Zhang. Dietary intake of phytoestrogens and the risk of prostate cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1884. doi:10.1158/1538-7445.AM2015-1884

Observational studies report inconsistent associations of fat and fatty acids with prostate cancer. We investigated associations between dietary fats and fatty acids and risk of prostate cancer in the NIH-American Association of Retired Persons (AARP) Diet and Health Study. Diet was assessed at baseline with self-administered food-frequency questionnaires. Cases were determined by linkage with state cancer registries. HR and 95% confidence intervals (CI) were estimated with Cox proportional hazards models. Among 288,268 men with average follow-up of nine years, 23,281 prostate cancer cases (18,934 nonadvanced and 2,930 advanced including 725 fatal cases) were identified. Total fat and mono- and polyunsaturated fat intakes were not associated with incidence of prostate cancer. Saturated fat intake was related to increased risk of advanced prostate cancer (HRQuintile 5 vs. Qunitile 1 (Q1 vs. Q5), 1.21; 95% CI, 1.00-1.46; Ptrend = 0.03) and fatal prostate cancer (HRQ5 vs. Q1, 1.47; 95% CI, 1.01-2.15; Ptrend = 0.04). α-Linolenic acid (ALA) intake was related to increased risk of advanced prostate cancer (HRQ5 vs. Q1, 1.17; 95% CI, 1.04-1.31; Ptrend = 0.01). Eicosapentanoic acid (EPA) intake was related to decreased risk of fatal prostate cancer (HRQ5 vs. Q1, 0.82; 95% CI, 0.64-1.04; Ptrend = 0.02). Our study suggests that the associations of fat and fatty acids differ by prostate cancer severity. Saturated fat, ALA, and EPA intakes were related to the risk of advanced or fatal prostate cancer but not to nonadvanced prostate cancer. Identifying factors associated with advanced prostate cancer could reduce morbidity and mortality.

The aim of the present study was to examine the association between intake of folate, and specific folate vitamers, and the risk of advanced and total prostate cancer. The association between dietary folate and prostate cancer risk was evaluated in The Netherlands Cohort Study (NLCS) on diet and cancer, conducted among 58,279 men ages 55-69 years at baseline. Information on diet was collected at baseline by means of food frequency questionnaires. Incident cases were identified by record linkage with regional cancer registries and the Dutch National Database of Pathology Reports. After 17.3 years of follow-up, 3,669 incident prostate cancer cases, of which 1,290 advanced cases, and 2,336 male subcohort members were available for case-cohort analyses. Dietary folate was not associated with prostate cancer risk, nor with the risk of advanced prostate cancer, among men in the NLCS cohort (HR = 1.05, 95 % CI: 0.87-1.26 and HR = 1.09, 95 % CI: 0.88-1.35, respectively, for the highest quintile of folate intake vs. the lowest quintile). Specific folate vitamers were neither associated with the risk of prostate cancer or risk of advanced prostate cancer. Our results do not support an association of dietary folate or specific folate vitamers on the risk of prostate cancer, or advanced prostate cancer.

Prostate cancer is one of the most common cancers worldwide. The etiology of prostate cancer largely remains unclear, with almost all established risk factors (e.g. age, race, family history) being not modifiable. Ecological, migrant, and temporal trend studies suggest that diet plays role in the occurrence of prostate cancer, but few nutrients that alter its risk have been identified from case-control and cohort studies. Vitamin K has two forms that naturally occur in foods, i.e., phylloquinone (vitamin K1) and menaquinone (vitamin K2). While phylloquinone is abundant in green leafy vegetables and some vegetable oils, menaquinone is primarily derived from fermented food products (e.g. cheese). Although experimental studies have shown that vitamin K inhibits the growth of various cancer cell lines (including prostate cancer cells), only one epidemiologic study has investigated the association between vitamin K intake and prostate cancer risk. In that German study, a significant inverse association with advanced prostate cancer was observed for menaquinone intake. The present study thus sought to investigate the associations between intake of vitamin K (from both dietary and supplemental sources) and the risk of total and advanced prostate cancer among 28,356 PLCO participants. A total of 2978 cases of prostate cancer (including 490 advanced cases) have been documented during a median follow up of 11.8 years. Advanced prostate cancer were defined as disease in stage II with a Gleason score of 8-10, stage III, or stage IV. Usual dietary intake among study subjects was assessed with Dietary Questionnaire (DQX) at baseline and Dietary History questionnaire (DHQ) at year 3, both of which were developed and validated by the National Cancer Institute. Dietary intake of phylloquinone and menaquinones were calculated using the USDA National Nutrient Database for Standard Reference (Release 23), supplemented with menaquinone data from published studies. Cox proportional hazards regression was performed to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for dietary intake of phylloquinone and menaquinones in relation to prostate cancer risk. After adjustment for confounders, no statistically significant associations were found between vitamin K intake estimated from the DQX and prostate cancer risk [HR (95% CI) for the highest quintile vs. the lowest quintile: 0.99 (0.87, 1.13) for total vitamin K, 0.99 (0.87, 1.12) for phylloquinone, and 1.02 (0.87, 1.18) for total menaquinones]. Overall null results were also observed when additional analysis was carried out by the stage of the disease (i.e. advanced and non-advanced cases) and for vitamin K intake data assessed with the DHQ. In summary, the present study revealed that intake of total vitamin K and its two natural forms was not associated with the risk of total and advanced prostate cancer. Citation Format: Maggie Hoyt, Michael Reger, Jianjun Zhang. No association between vitamin K intake and prostate cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5312. doi:10.1158/1538-7445.AM2017-5312

Studies suggest a decreased risk of high-grade prostate cancer in men with lower circulating total cholesterol and that statins may protect against aggressive disease. Confirmation in additional populations and examination of associations for lipoprotein subfractions are needed. We examined prostate cancer risk and serum total and HDL cholesterol in the ATBC Study cohort (n=29,093). Cox proportional hazards models were used to estimate the relative risk of total (n=2,041), non-aggressive (n=829), aggressive (n=461), advanced (n=412), and high-grade (n=231) prostate cancer by categories of total and HDL cholesterol. After excluding the first 10years of follow-up, men with higher serum total cholesterol were at increased risk of overall (≥240 vs. <200mg/dl: HR=1.22, 95% CI 1.03-1.44, p-trend=0.01) and advanced (≥240 vs. <200mg/dl: HR=1.85, 95% CI 1.13-3.03, p-trend=0.05) prostate cancer. Higher HDL cholesterol was suggestively associated with a decreased risk of prostate cancer regardless of stage or grade. In this population of smokers, high serum total cholesterol was associated with higher risk of advanced prostate cancer, and high HDL cholesterol suggestively reduced the risk of prostate cancer overall. These results support previous studies and, indirectly, support the hypothesis that statins may reduce the risk of advanced prostate cancer by lowering cholesterol.

A Prospective Study of the Association between Physical Activity and Risk of Prostate Cancer Defined by Clinical Features and TMPRSS2:ERG

It is unknown whether alcohol intake is associated with the risk of lethal (metastatic or fatal) prostate cancer. We examine (1) whether alcohol intake among men at risk of prostate cancer is associated with diagnosis of lethal prostate cancer and (2) whether intake among men with nonmetastatic prostate cancer is associated with metastasis or death. This prospective cohort study uses the Health Professionals Follow-Up Study (1986 to 2012). Our analysis of alcohol intake among men at risk of prostate cancer included 47,568 cancer-free men. Our analysis of alcohol intake among men with prostate cancer was restricted to 5,182 men diagnosed with nonmetastatic prostate cancer during follow-up. We examine the association of total alcohol, red and white wine, beer, and liquor with lethal prostate cancer and death. Multivariate Cox proportional hazards regression estimated hazard ratios (HRs) and 95% CIs. Alcohol drinkers had a lower risk of lethal prostate cancer (any v none: HR, 0.84 [95% CI, 0.71 to 0.99]) without a dose-response relationship. Total alcohol intake among patients with prostate cancer was not associated with progression to lethal prostate cancer (any v none: HR, 0.99 [95% CI, 0.57 to 1.72]), whereas moderate red wine intake was associated with a lower risk (any v none: HR, 0.50 [95% CI, 0.29 to 0.86]; P trend = .05). Compared with none, 15 to 30 g/d of total alcohol after prostate cancer diagnosis was associated with a lower risk of death (HR, 0.71 [95% CI, 0.50 to 1.00]), as was red wine (any v none: HR, 0.74 [95% CI, 0.57 to 0.97]; P trend = .007). Cancer-free men who consumed alcohol had a slightly lower risk of lethal prostate cancer compared with abstainers. Among men with prostate cancer, red wine was associated with a lower risk of progression to lethal disease. These observed associations merit additional study but provide assurance that moderate alcohol consumption is safe for patients with prostate cancer.

Background: A growing body of research has shown the benefits of a healthy diet on a variety of cancer outcomes. Evidence is inconsistent for prostate cancer and research in diverse populations is limited. Methods: In the Multiethnic Cohort Study (MEC), we conducted a prospective cohort analysis to investigate the association of four diet quality indices (DQIs; AHEI-2010, aMED, HEI-2015, DASH; a higher score indicates healthier diet), three plant-based diet indices (PDI, hPDI, uPDI), two inflammatory (DII, EDIP), and two insulinemic dietary indices (EDIH, EDIR) (a higher score indicates more pro-inflammatory or pro-insulinemic diet) with incidence of prostate cancer (PCa) in 79,930 men from five racial/ethnic groups (White, African American, Japanese American, Latino, and Native Hawaiian). All dietary scores were constructed from a baseline quantitative food frequency questionnaire. Outcomes examined included total PCa, high-grade PCa (Gleason score &amp;gt; 7), advanced PCa (regional or distant), aggressive PCa (high-grade or advanced), and lethal PCa (distant or death due to PCa). Hazard ratios (HR) and 95% confidence intervals (CI) per one standard deviation (SD) increase in the dietary score were estimated from Cox proportional hazards models, overall and by race/ethnicity. Associations were considered nominally significant at P &amp;lt; 0.05. Results: During a mean follow-up of 18.9 years, a total of 9,759 incident PCa cases were identified, including 2,503 high-grade, 1,706 advanced, 3,430 aggressive, and 1,426 lethal PCa cases. None of the dietary scores was significantly associated with total PCa. We found a significant association between DII and advanced PCa (HR=1.08, 95% CI=1.01-1.15) overall and the association appeared to be the strongest in African Americans (HR=1.17, 95% CI=1.00-1.36) and Native Hawaiians (HR=1.29, 95% CI=0.98-1.68). We also observed weak associations of the four DQIs with advanced PCa (HR of 0.95-0.96, P of 0.07-0.10) in the overall population, among which a higher DASH score was significantly associated with a 15% (95% CI = 0.75-0.96) lower risk of advanced PCa in African Americans. In addition, we observed that several inflammatory (EDIP) and insulinemic (EDIH, EDIR) dietary scores were associated with lower incidence of advanced, aggressive, or lethal PCa (HR=0.89-0.95, P of 0.03-0.05), which requires further investigation. Conclusions: Our findings suggest that diets with high proinflammatory potential may increase risk of advanced PCa while following a healthy dietary pattern may reduce the risk of advanced PCa. Further studies are needed to better understand the inconsistent results across studies on diet and PCa risk and whether our findings can be replicated in other populations. Citation Format: Wei Xiong, Song-Yi Park, Anqi Wang, Peggy Wan, Lynne R. Wilkens, Loïc Le Marchand, Christopher A. Haiman, Fei Chen. Dietary patterns and prostate cancer risk in the Multiethnic Cohort Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2203.

Prostate cancer and urinary bladder cancer are frequently occurring cancers with few risk factors identified. We examined the relation of Mediterranean diet (MD) adherence with risks of prostate and bladder cancer in the Netherlands Cohort Study (NLCS). Data were available for 58,279 men and 62,573 women, who completed a baseline questionnaire on diet and other cancer risk factors. Multiple MD scores, including the alternate Mediterranean diet score without alcohol (aMEDr), were calculated to assess MD adherence. After 20.3 years of follow-up, 3,868 prostate cancer cases (advanced: 1,256) and 1,884 bladder cancer cases could be included in multivariable Cox proportional hazards analyses. aMEDr was not associated with advanced prostate cancer risk [hazard ratio (HR)per 2-point increment (95% confidence interval, 95% CI) = 1.06 (0.96-1.17)]. In contrast, higher aMEDr values were associated with a significantly increased risk of nonadvanced prostate cancer (P trend = 0.04). For bladder cancer risk, no association was observed with aMEDr [HRper 2-point increment (95% CI) = 1.00 (0.92-1.09)]. Absolute scores based on the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) dietary recommendations were not associated with prostate or bladder cancer risk. MD adherence, measured by aMEDr or other MD scores, was not associated with decreased risks of advanced prostate cancer and bladder cancer in the NLCS. Higher levels of care-seeking behavior, screening attendance, and prostate cancer awareness in higher educated men with healthier lifestyles could potentially explain the positive associations observed for nonadvanced prostate cancer risk. MD adherence does not seem to reduce the risk of (advanced) prostate cancer or bladder cancer.

Introduction: Selenium status has been associated with a reduced risk of total prostate cancer (PCa) and there is evidence that the association is more pronounced for advanced, clinically relevant PCa. This association, however, has been studied over a relatively narrow range of selenium status and data from low-selenium populations are missing. Most prior studies of selenium status and PCa have used plasma/serum selenium, which reflects recent selenium intake, and few studies have used toenail selenium, which reflects longer exposure time windows. Methods: We studied the association of toenail selenium and advanced PCa risk in the Netherlands Cohort study, which includes 58,279 men aged 55 to 69 years. The study has a case-cohort design; a random subcohort was sampled at baseline in 1986 and incident advanced (stage III/IV) PCa cases were identified during 17.3 years of follow-up. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression models. Results: The study population included 898 advanced PCa cases and 1,203 subcohort members. The average toenail selenium concentration among subcohort members was 0.549 μg/g (standard deviation: 0.128). Toenail selenium was associated with a reduced risk of advanced PCa and adjusted HRs for increasing quintiles of toenail selenium were 1.00 (reference), 0.69 (95% CI: 0.52, 0.90), 0.45 (95% CI: 0.34, 0.60), 0.32 (95% CI: 0.24, 0.44), and 0.24 (95% CI: 0.17, 0.33) (P for trend &amp;lt;0.01). The association was more pronounced for men diagnosed during later follow-up, and adjusted HRs (0.045 μg/g increment; size central quintile) for men diagnosed during ≤6 years, &amp;gt;6 to 12 years, and &amp;gt;12 years of follow-up were 0.91 (95% CI: 0.85, 0.98), 0.85 (95% CI: 0.75, 0.96), and 0.77 (95% CI: 0.71, 0.84), respectively. Conclusion: Toenail selenium was associated with a substantial decrease in risk of advanced PCa, particularly during later follow-up. If our results can be confirmed, a prevention trial of selenium and PCa in a low-selenium population may be justified. Selenium exerts important biological functions through its presence in selenoproteins and genetic variation in the major selenoproteins glutathione peroxidase 1 (GPX1) and selenoprotein P (SEPP1) has been associated with the risk of PCa. In a next analysis, in the same population, we will study the association of common variation in GPX1 and SEPP1 with advanced PCa risk, and we will evaluate SNP-selenium interactions. Citation Format: Milan S. Geybels, Bas A.J. Verhage, Frederik J. van Schooten, Alexandra Goldbohm, Piet A. van den Brandt. Toenail selenium is associated with a decreased risk of advanced prostate cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3613. doi:10.1158/1538-7445.AM2013-3613

Background: Studies of diet and prostate cancer have primarily focused on individual dietary factors, often with null or mixed findings. Assessment of dietary patterns is an alternative approach and has been increasingly used in nutritional epidemiology, providing the advantage of better accounting for added effects and interactions of dietary components. Hyperinsulinemia and inflammation are interrelated biological pathways that link diet with risk of several cancers, and studies have suggested that these may also increase prostate cancer risk. Whether dietary patterns based on these pathways contribute to the development and progression of prostate cancer is unclear. Methods: We followed 39,776 men in the Health Professionals Follow-up Study (1986-2014) to examine associations between two empirical hypothesis-oriented dietary patterns with risk of total, local, advanced, and fatal prostate cancer. The two dietary patterns - empirical dietary index for hyperinsulinemia (EDIH) and empirical dietary inflammatory pattern (EDIP) - were constructed using the weighted sum of food groups that predicted plasma C-peptide (EDIH) and inflammatory biomarkers (EDIP). Dietary scores were calculated from food frequency questionnaires at baseline and updated every 4 years. Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression. Results: We documented 5,682 incident cases of total prostate cancer and 658 cases of fatal prostate cancer over 868,552 person-years of follow-up. In multivariable-adjusted models, men in the highest EDIH quintile had an 18% higher risk of advanced prostate cancer (HR: 1.18, 95% CI: 0.96-1.45; P=0.04 for trend) and a 24% higher risk of fatal prostate cancer (HR: 1.24, 95% CI: 0.96-1.59; P=0.03 for trend) compared to men in the lowest quintile. There were no significant associations for EDIP and prostate cancer risk. BMI did not modify the association for either dietary pattern. Conclusion: Hyperinsulinemia may be a potential mechanism linking dietary patterns and risk of aggressive prostate cancer. Additional studies to define mechanisms of action and interventions to reduce prostate cancer risk are warranted. Citation Format: Benjamin C. Fu, Fred K. Tabung, Claire H. Pernar, Weike Wang, Amparo G. Gonzalez-Feliciano, Ilkania M. Chowdhury-Paulino, Steven K. Clinton, Edmund Folefac, Mingyang Song, Adam S. Kibel, Edward L. Giovannucci, Lorelei A. Mucci. Insulinemic and inflammatory dietary patterns and risk of prostate cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4648.

Introduction: The association between tobacco smoking and prostate cancer (PCa) risk and progression remains unclear. This study examined the association between tobacco smoking and risk of localized and advanced PCa, PCa-specific mortality, and overall mortality in African-American, Hispanic and non-Hispanic White men. Polymorphisms in xenobiotic metabolism enzyme genes were further examined as possible modifiers of associations with smoking. Methods: Using data from the California Collaborative Prostate Cancer Study, a multiethnic population-based case-control study conducted in Los Angeles County (631 advanced and 533 localized cases; 594 controls) and the San Francisco Bay Area (568 advanced and 208 localized cases; 545 controls), we evaluated associations between tobacco smoking and risk of localized and advanced PCa using conditional logistic regression. Cox proportional hazards regression models and Kaplan Meier curves with log-rank tests were used to assess associations with PCa-specific and all-cause mortality. Median follow-up time for cases was 8.8 years (IQR: 6.2-9.9). We also investigated the role of 12 metabolism enzyme single nucleotide polymorphisms from 7 genes as potential modifiers of the relationship between tobacco smoking and PCa risk and progression using interaction models. Results: After adjusting for age, PCa family history, body mass index, alcohol consumption, intake of meat cooked at high temperature, and use of snuffing/chewing tobacco, non-Hispanic Whites who were former smokers had an increased risk of localized PCa when compared to never smokers (OR=1.52, 95%CI: 1.11-2.09, p&amp;lt;0.01). Risk increased with younger age at first tobacco use (p-trend&amp;lt;0.01), duration of tobacco smoking (p-trend=0.01), number of daily cigarettes smoked (p-trend=0.02), and cigarette pack-years (p-trend=0.03). Current smoking was associated with an increased risk of advanced PCa (OR=1.41, 95%CI: 1.02-1.94, p=0.037) among non-Hispanic Whites, but a decreased risk among Hispanics (OR=0.48, 95%CI: 0.23-0.99, p=0.047). No significant trends were seen for any of the smoking variables among Hispanics or African-Americans. A CYP1A2 polymorphism (rs7662551) modified the relationship between smoking status and PCa risk; the addition of each C-allele increased risk for localized (p-interaction=0.01) and advanced (p-interaction=0.03) PCa, particularly among current smokers. Tobacco smoking was not associated with PCa-specific mortality. For all-cause mortality, increased risk was associated with current smoking, duration of smoking, cigarette pack-years, and young age at first smoking. Kaplan Meier survival probabilities for current smokers were 77% from all-cause mortality and 89% from PCa-specific mortality. Conclusions: We observed that tobacco smoking was associated with risk of localized and advanced PCa primarily among Non-Hispanic Whites. Moreover, we observed that tobacco smoking was associated with all-cause mortality, albeit no associations were observed for PCa-specific mortality. Genetic variation in CYP1A2 seems to modify the relationship of tobacco smoking status and PCa risk, but not mortality. Citation Format: Ahva Shahabi, Roman Corral, Chelsea Catsburg, Amit D. Joshi, Jocelyn Koo, Esther M. John, Sue A. Ingles, Mariana C. Stern. Tobacco smoking, polymorphisms in xenobiotic metabolism enzyme genes, and prostate cancer risk and survival. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr B79.

The reasons behind socio-economic disparities in prostate cancer incidence remain unclear. We tested the hypothesis that individual-level factors act jointly with neighborhood-level social and built environment factors to influence prostate cancer risk and that specific social and built environment factors contribute to socio-econmic differences in risk. We used multi-level data, combining individual-level data (including education and known prostate cancer risk factors) for prostate cancer cases (n = 775) and controls (n = 542) from the San Francisco Bay Area Prostate Cancer Study, a population-based case-control study, with contextual-level data on neighborhood socio-economic status (nSES) and specific social and built environment factors from the California Neighborhoods Data System. Multivariable logistic regression models were used to compute adjusted odds ratios separately for localized and advanced stage prostate cancer while controlling for neighborhood clustering. We found a more than twofold increased risk of both localized and advanced prostate cancer with increasing levels of nSES, and decreased risk of advanced prostate cancer with increasing levels of education. For localized disease, the nSES association was largely explained by known prostate cancer risk factors and specific neighborhood environment factors; population density, crowding, and residential mobility. For advanced disease, associations with education and nSES were not fully explained by any available individual- or neighborhood-level factors. These results demonstrate the importance of specific neighborhood social and built environment factors in understanding risk of localized prostate cancer. Further research is needed to understand the factors underpinning the associations between individual- and neighborhood-level SES and risk of advanced prostate cancer.