Milan S. Geybels

Statin use in relation to prostate cancer outcomes in a population-based patient cohort study.

We investigated associations between statin use begun before prostate cancer (PCa) diagnosis and PCa recurrence/progression and PCa‐specific mortality (PCSM) in a prospective, population‐based cohort study.

Dietary Flavonoid Intake, Black Tea Consumption, and Risk of Overall and Advanced Stage Prostate Cancer

Flavonoids are natural antioxidants found in various foods, and a major source is black tea. Some experimental evidence indicates that flavonoids could prevent prostate cancer. We investigated the associations between flavonoid intake, black tea consumption, and prostate cancer risk in the Netherlands Cohort study, which includes 58,279 men who provided detailed baseline information on several cancer risk factors. From 1986 to 2003, 3,362 prostate cancers were identified, including 1,164 advanced (stage III/IV) cancers. Cox proportional hazards regression using the case-cohort approach was used to estimate hazard ratios and 95% confidence intervals. Intake of total catechin, epicatechin, kaempferol, and myricetin and consumption of black tea were associated with a decreased risk of stage III/IV or stage IV prostate cancer. Hazard ratios of stage III/IV and stage IV prostate cancer for the highest versus the lowest category of black tea consumption (≥5 versus ≤1 cups/day) were 0.75 (95% confidence interval: 0.59, 0.97) and 0.67 (95% confidence interval: 0.50, 0.91), respectively. No associations were observed for overall and nonadvanced prostate cancer. In conclusion, dietary flavonoid intake and black tea consumption were associated with a decreased risk of advanced stage prostate cancer.

Advanced prostate cancer risk in relation to toenail selenium levels.

BACKGROUNDnSelenium may prevent advanced prostate cancer (PCa), but most studies on this topic were conducted in populations with moderate to high selenium status. We investigated the association of toenail selenium, reflecting long-term selenium exposure, and advanced PCa risk in a population from the Netherlands where low selenium status is widespread.nnnMETHODSnThe analysis was conducted in the prospective Netherlands Cohort Study, which included 58 279 men aged 55 to 69 years at baseline in 1986. All cohort members completed a baseline questionnaire, and approximately 79% of participants provided toenail clippings, which were used for toenail selenium measurements using instrumental neutron activation analysis. Incident advanced PCa case subjects from the entire cohort were identified during 17.3 years of follow-up. The study employed a case-cohort design for which a random subcohort was sampled at baseline. Hazard ratios and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression models. All tests were two-sided.nnnRESULTSnComplete toenail selenium data were available for 898 advanced (International Union Against Cancer stage III/IV) PCa case subjects and 1176 subcohort members. The average toenail selenium concentration of subcohort members was 0.550 µg/g. Toenail selenium was associated with a reduced risk of advanced PCa; adjusted hazard ratio for the highest vs lowest quintile was 0.37 (95% CI = 0.27 to 0.51; P trend < .001). For stage IV PCa, men in the highest vs lowest quintile of toenail selenium had an adjusted hazard ratio of 0.30 (95% CI = 0.21 to 0.45; P trend < .001).nnnCONCLUSIONSnToenail selenium was associated with a substantial decrease in risk of advanced PCa.

Selenoprotein Gene Variants, Toenail Selenium Levels, and Risk for Advanced Prostate Cancer

Lower selenium levels have been associated with increased risk of prostate cancer (PCa), and genetic variation in the selenoprotein genes selenoprotein P (SEPP1) and glutathione peroxidase 1 (GPX1) is thought to modify this relationship. We investigated whether the association between toenail selenium levels and advanced PCa risk in the prospective Netherlands Cohort Study is modified by common genetic variation in SEPP1 and GPX1. Toenail clippings were used to determine selenium levels and to isolate DNA for genotyping. This case-cohort study, which included 817 case subjects with advanced PCa and 1048 subcohort members, was analyzed with Cox regression models. All statistical tests were two-sided. Three genetic variants were associated with advanced (stage III/IV or IV) PCa risk: SEPP1 rs7579 (lower risk; P trend = .01), GPX1 rs17650792 (higher risk; P trend = .03), and GPX1 rs1800668 (lower risk; P trend = .005). Toenail selenium levels were inversely associated with advanced PCa risk, independently of common genetic variation in SEPP1 and GPX1.

Variation in selenoenzyme genes and prostate cancer risk and survival.

While several studies showed that selenium may prevent prostate cancer (PCa), few studies have evaluated variation in selenoenzyme genes in relation to PCa risk and survival.

Associations of tea and coffee consumption with prostate cancer risk

PurposeTea and coffee contain bioactive compounds and both beverages have recently been associated with a reduced risk of prostate cancer (PCa).MethodsWe studied associations of tea and coffee consumption with PCa risk in a population-based case–control study from King County, Washington, USA. Prostate cancer cases were diagnosed in 2002–2005 and matched to controls by 5-year age groups. Logistic regression was used to generate odds ratios (ORs) and 95xa0% confidence intervals (CIs).ResultsAmong controls, 19 and 58xa0% consumed at least one cup per day of tea and coffee, respectively. The analysis of tea included 892 cases and 863 controls, and tea consumption was associated with a reduced overall PCa risk with an adjusted OR of 0.63 (95xa0% CI: 0.45, 0.90; P for trendxa0=xa00.02) for men in the highest compared to lowest category of tea intake (≥2 cups/day vs. ≤1 cup/week). Risk estimates did not vary substantially by Gleason grade or disease stage. Coffee consumption was not associated with risk of overall PCa or PCa in subgroups defined by tumor grade or stage.ConclusionsOur results contribute further evidence that tea consumption may be a modifiable exposure that reduces PCa risk.

Oxidative stress-related genetic variants, pro- and antioxidant intake and status, and advanced prostate cancer risk

Background: Increased oxidative stress has been linked to prostate cancer. We investigated oxidative stress–related genetic variants in relation to advanced prostate cancer risk and examined potential interactions with pro- and antioxidant exposures. Methods: A case-cohort analysis was conducted in the prospective Netherlands Cohort Study, which included 58,279 men ages 55 to 69 years. Cohort members completed a baseline questionnaire and provided toenail clippings, which were used to isolate DNA. Advanced prostate cancer cases were identified during 17.3 years of follow-up. The analysis included 14 genetic variants and 11 exposures. Cox regression models were used for analysis and FDR Q-values were calculated. Results: Complete genotyping data were available for 952 cases and 1,798 subcohort members. CAT rs1001179 was associated with stage III/IV and stage IV prostate cancer risk, with HRs per minor allele of 1.16 [95% confidence intervals (CI), 1.01–1.33; P = 0.032] and 1.25 (95% CI, 1.07–1.46; P = 0.006), respectively. We tested 151 gene–environment interactions in relation to both stage III/IV and IV prostate cancer risk. Seven interactions were statistically significant after adjusting for multiple testing (FDR Q-value <0.20); for stage III/IV prostate cancer, these involved intake of β-carotene (GPX1 rs17650792, hOGG1 rs1052133) and heme iron (GPX1 rs1800668 and rs3448), and for stage IV prostate cancer, these involved intake of catechin (SOD2 rs4880) and heme iron (hOGG1 rs1052133, SOD1 rs10432782). Conclusion: This study of advanced prostate cancer risk showed a marginal association with a CAT polymorphism and seven novel gene–environment interactions in the oxidative stress pathway. Impact: Oxidative stress–related genes and exposures may have a joint effect on advanced prostate cancer. Cancer Epidemiol Biomarkers Prev; 24(1); 178–86. ©2014 AACR.

Coffee and tea consumption in relation to prostate cancer prognosis

BackgroundBioactive compounds found in coffee and tea may delay the progression of prostate cancer.MethodsWe investigated associations of pre-diagnostic coffee and tea consumption with risk of prostate cancer recurrence/progression. Study participants were men diagnosed with prostate cancer in 2002–2005 in King County, Washington, USA. We assessed the usual pattern of coffee and tea consumption two years before diagnosis date. Prostate cancer-specific outcome events were identified using a detailed follow-up survey. Multivariable Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95xa0% confidence intervals (CIs).ResultsThe analysis of coffee intake in relation to prostate cancer recurrence/progression included 630 patients with a median follow-up of 6.4xa0years, during which 140 prostate cancer recurrence/progression events were recorded. Approximately 61xa0% of patients consumed at least one cup of coffee per day. Coffee consumption was associated with a reduced risk of prostate cancer recurrence/progression; the adjusted HR for ≥4xa0cups/day versus ≤1xa0cup/week was 0.41 (95xa0% CI: 0.20, 0.81; p for trendxa0=xa00.01). Approximately 14xa0% of patients consumed one or more cups of tea per day, and tea consumption was unrelated to prostate cancer recurrence/progression.ConclusionResults indicate that higherxa0pre-diagnostic coffee consumption is associated with a lower risk of prostate cancer recurrence/progression. This finding will require replication in larger studies.

Measures of combined antioxidant and pro-oxidant exposures and risk of overall and advanced stage prostate cancer

PURPOSEnOxidative stress is possibly related to prostate carcinogenesis. We constructed a dietary antioxidant score, which is a measure of combined antioxidant exposures, and an oxidative balance score (OBS), which is a measure of combined antioxidant and pro-oxidant exposures. We hypothesized that both scores are inversely associated with the risk of prostate cancer (PCa).nnnMETHODSnWe conducted a case-cohort study among 58,279 men in the Netherlands Cohort Study. Cohort members completed a baseline questionnaire. From 1986 to 2003, 3451 patients with PCa were identified including 1196 advanced cancers (stage III/IV). The antioxidant score and the OBS were created by summing quartile and category scores of individual score constituents, which had an equal weight. Pro-oxidants were scored in the opposite way to antioxidants.nnnRESULTSnBoth the antioxidant score and OBS were not associated with risk of overall PCa or PCa subgroups on the basis of disease stage. Most score constituents were not associated with the risk of PCa. Total catechin intake was associated with a decreased risk of stage IV PCa (greatest vs. lowest quartile: hazard ratio, 0.76; 95% confidence interval, 0.59-0.98).nnnCONCLUSIONSnThe antioxidant score and OBS were not associated with risk of overall and advanced-stage PCa.

Abstract 3613: Toenail selenium is associated with a decreased risk of advanced prostate cancer.

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DCnnIntroduction: 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 6 to 12 years, and >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.nnCitation 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