Risk Of Total Prostate Cancer Research Articles

Abstract 1915: Specialty supplements and prostate cancer risk in the vitamins and lifestyle (VITAL) cohort

Abstract Although there is evidence from studies of prostate cancer cell lines and rodent models that several supplements may have anti-inflammatory, anti-oxidant, or other anti-cancer properties, few epidemiologic studies have examined the association between non-vitamin, non-mineral, specialty supplement use and prostate cancer risk. Participants, 50-76 years, were 35,239 male members of the VITamins And Lifestyle (VITAL) cohort who were residents of western Washington State, and who completed an extensive baseline questionnaire in 2000-2002. Participants responded about their frequency (days/week) and duration (years) of specialty supplement uses. 1,602 incident invasive prostate cancers were obtained from the Surveillance, Epidemiology, and End Results registry. Multivariate-adjusted hazards ratios (HR) and 95% confidence intervals (95% CI) were estimated by Cox proportional hazards models. Any use of grapeseed supplements was associated with a 41% (HR 0.59, 95% CI: 0.40-0.86) reduced risk of total prostate cancer. Although not statistically different, the association was somewhat stronger for low-grade (HR 0.58, 95% CI: 0.33-1.03) than high-grade tumors (HR 0.82, 95% CI: 0.34-2.00). There were no associations for use of chondroitin, co-enzyme Q10, fish oil, garlic, ginkgo biloba, ginseng, glucosamine, or saw palmetto. Grapeseed may be a potential chemopreventive agent, however as current evidence is limited, it should not yet be promoted for prevention of prostate cancer. This work is supported by NCI grants R25-CA94880, R01-CA142545, and K05-CA154337 Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1915. doi:10.1158/1538-7445.AM2011-1915

Serum retinol and risk of prostate cancer.

Greater exposure to retinol (vitamin A) may prevent prostate cancer, although under some conditions it could promote cell growth and de-differentiation. The authors prospectively examined prostate cancer risk and serum retinol levels, measured by using high-performance liquid chromatography, at baseline (n = 29,104) and after 3 years (n = 22,843) in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort. Cox proportional hazards models were used to estimate the relative risk of total (n = 2,041) and aggressive (n = 461) prostate cancer by quintiles of baseline and 3-year serum retinol concentrations and by change in serum retinol levels from baseline to 3 years. Men with higher retinol concentrations at baseline were more likely to develop prostate cancer (quintile 5 vs. quintile 1 hazard ratio = 1.19, 95% confidence interval: 1.03, 1.36; P(trend) = 0.009). The results were similar for aggressive disease. Joint categorization based on baseline and 3-year retinol levels showed that men who were in the highest quintile at both time points had the greatest increased risk (baseline/3-year quintile 5/quintile 5 vs. quintile 1/quintile 1 hazard ratio = 1.31, 95% confidence interval: 1.08, 1.59). In this largest study to date of vitamin A status and subsequent risk of prostate cancer, higher serum retinol was associated with elevated risk, with sustained high exposure conferring the greatest risk. Future studies may clarify the underlying biologic mechanisms of the retinol-prostate cancer association.

Long‐term aspirin use and the risk of total, high‐grade, regionally advanced and lethal prostate cancer in a prospective cohort of health professionals, 1988–2006

Experimental studies suggest a role for aspirin in the chemoprevention of prostate cancer and epidemiological evidence supports a modest inverse association between regular aspirin use and prostate cancer risk, especially for advanced disease. In a prospective cohort study of 51,529 health professionals aged 40-75 years at baseline, we evaluated long-term aspirin use and the incidence of total, high-grade (Gleason 8-10, n = 488), regionally advanced (T3b-T4 or N1, n = 228) and lethal prostate cancer (M1, bony metastases or prostate cancer death, n = 580) from 1988-2006. We used Cox proportional hazards regression to evaluate risk associated with frequency (days/week), quantity (tablets/week), recency and duration of aspirin use after multivariable adjustment for confounders and other predictors of prostate cancer risk. A total of 4,858 men were diagnosed with prostate cancer during the 18-year study period. Men taking ≥ 2 adult-strength aspirin tablets a week had a 10% lower risk of prostate cancer (p-for-trend = 0.02). For regionally advanced cancer, we observed no significant associations with aspirin use. For high-grade and lethal disease, men taking ≥ 6 adult-strength tablets/week experienced similar reductions in risk hazard ratio [HR = 0.72 (95% confidence intervals [CI]: 0.54, 0.96) and HR = 0.71 (95% CI: 0.50, 1.00)]. Analytical approaches to address bias from more frequent prostate-specific antigen screening among aspirin users did not yield different conclusions. We observed reductions in the risk of high-grade and lethal prostate cancer associated with higher doses of aspirin, but not with greater frequency or duration, in a large, prospective cohort of health professionals. Our data support earlier observations of modest inverse associations with advanced prostate cancer.

Association between p53 Pro72Arg polymorphism and prostate cancer risk: a meta-analysis

The tumor suppressor gene p53 appears to be important in the development of many human cancers, such as prostate cancer. The association of p53 codon72 polymorphism with prostate cancer has been widely reported; however, the results are inconsistent. To derive a more precise estimation of this relationship, we performed an updated meta-analysis from 10 case-control studies. We conducted a search in the PubMed database without a language limitation, covering all papers published until July 2010. Risk ratios (RR) with 95%confidence intervals (CIs) were used to assess the strength of the association. Ten studies including 1,196 cases and 1,704 controls were selected. Overall, no significant differences of total prostate cancer risk and p53 codon polymorphism was found (Pro/Pro vs Arg/Arg, RR = 1.12, 95%CI=0.74-1.70, Pheterogeneity = 0.016, I2 = 55.8%; Pro/Pro+Pro/Arg vs Arg/Arg, RR = 1.05, 95%CI=1.00-1.11, Pheterogeneity = 0.077, I2 = 51.1%). In the stratified analysis by ethnicity, the same results were found. However, in the control subgroup, there was a modest decreased association between prostate cancer risk and population-based control subjects under the recessive genetic model (RR = 0.31, 95%CI=0.10-0.91, Pheterogeneity = 0.110, I2 =60.8%). This meta-analysis suggested that p53 codon Pro72Arg polymorphism could be weakly associated with prostate cancer risk.

Dietary glycemic index, glycemic load, insulin index, fiber and whole-grain intake in relation to risk of prostate cancer.

Insulin may play a role in prostate cancer tumorigenesis. Postprandial blood glucose and insulin responses of foods depend importantly on the carbohydrate quality and quantity, represented by glycemic index (GI), glycemic load (GL), fiber and whole-grain content, but are also influenced by intake of protein and other characteristics. The recently developed insulin index (II) quantifies the postprandial insulin secretion, also taking into account these additional characteristics. We investigated the association between dietary GI, GL, II, fiber, and whole grains and risk of total prostate cancer (n=5,112) and subgroups of prostate cancer as defined by stage or grade in 49,934 male participants of the Health Professionals Follow-up Study. Multivariate adjusted hazard ratios (HR) and 95% confidence intervals (95% CI) were estimated using Cox proportional hazards regression. Dietary GI, GL, II, or fiber was not associated with risk of total or subgroups of prostate cancer. We observed a positive association between dietary intake of whole grains and total prostate cancer (HR highest versus lowest quintile 1.13, 95% CI 1.03-1.24), which was attenuated after restriction to PSA-screened participants (HR 1.03, 95% CI 0.91-1.17). These results suggest that long-term exposure to a diet with a high insulin response does not affect prostate cancer incidence.

Urinary phytoestrogens and risk of prostate cancer in Jamaican men

We evaluated the relationship of spot urinary concentrations of phytoestrogens with total prostate cancer and tumor grade in a hospital-based case-control study in Jamaica. Urine samples were analyzed for genistein, daidzein, equol (isoflavones), and enterolactone (lignan) among newly diagnosed cases (n = 175) and controls (n = 194). Urinary concentrations of enterolactone (lignan) were higher among cases. There were no significant differences in median concentrations of isoflavone excretion. Compared with non-producers of equol (reference tertile), men who produced equol were at decreased risk of total prostate cancer (tertile 2: OR, 0.42; CI, 0.23-0.75) (tertile 3: OR, 0.48; CI, 0.26-0.87) (p (trend), 0.020) and high-grade disease (tertile 2: OR, 0.31; CI, 0.15-0.61) (tertile 3: OR, 0.29; CI, 0.13-0.60) (p (trend), 0.001). Higher concentrations of enterolactone were positively related to total prostate cancer (OR, 1.85; CI, 1.01-3.44; p (trend), 0.027) as well as high-grade disease (OR, 2.46; CI, 1.11-5.46; p (trend), 0.023). There were no associations between urinary excretion of genistein and daidzein with risk of prostate cancer. Producers of equol (isoflavone) may be at reduced risk of total- and high-grade prostate cancer whereas enterolactone may increase the likelihood of disease.

Arg462Gln and Asp541Glu polymorphisms in ribonuclease L and prostate cancer risk: a meta-analysis

Objective The association between ribonuclease L (RNASEL) gene polymorphisms and prostate cancer risk has been widely reported, but the results of these studies remained controversial and underpowered. We performed a meta-analysis of 28 studies to evaluate the association between Arg462Gln and Asp541Glu polymorphisms in the RNASEL gene and prostate cancer risk. Methods Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association between RNASEL polymorphisms and prostate cancer risk. Results A significantly increased prostate cancer risk was found for the Arg462Gln polymorphism in Africans (Gln/Gln vs Arg/Arg: OR = 2.50, 95%CI = 1.28–4.87; Gln/Gln vs Gln/Arg + Arg/Arg: OR = 2.54, 95%CI = 1.30–4.95), but not in Europeans and Asians. Additionally, the Asp541Glu polymorphism was associated with increased total prostate cancer risk (Glu-allele vs Asp-allele: OR = 1.04, 95%CI = 1.01–1.07; Glu/Glu vs Asp/Asp: OR = 1.22, 95%CI = 1.03–1.46; Glu/Glu vs Glu/Asp + Asp/Asp: OR = 1.09, 95%CI = 1.02–1.16). In the stratified analysis for the As-p541Glu polymorphism, there was a significantly increased prostate cancer risk in Africans and Europeans, and in hospital-based prostate cancer cases. Conclusion The meta-analysis results showed evidence that RNASEL Arg462Gln and Asp541Glu polymorphisms are associated with prostate cancer risk and could be low-penetrance prostate cancer susceptibility biomarkers.

Abstract 2823: Dietary glycemic index, glycemic load and insulin index, in relation to risk of prostate cancer

Abstract Background: The insulin and insulin-like growth factor (IGF) axis has been shown to play a role in prostate cancer tumorigenesis. Circulating IGF-1 and fasting insulin as well as insulin resistance have been associated with increased risk of total or advanced prostate cancer in some epidemiological studies. Through alterations by diet the insulin and IGF axis may be potentially modifiable. The dietary insulin response depends largely but not entirely on the quality and quantity of dietary carbohydrates. The glycemic index (GI) is a measure of the propensity of carbohydrate containing foods to raise blood glucose levels postprandially. The more recently developed food insulin index is a comparable measure which is based on the diet's effect on insulin secretion, also taking into account foods with low or no carbohydrate content. We hypothesized that high dietary glycemic index, glycemic load (GL) and insulin index (II) are associated with increased risk of prostate cancer. Material and Methods: We followed 47,779 Health Professionals Follow-up Study participants between 1986 and 2006 for prostate cancer incidence. Dietary intake was assessed by food frequency questionnaire (FFQ) in 1986 and updated every 4 years. Dietary GL was calculated by multiplying GI by the carbohydrate content and consumption frequency of each FFQ item and then summing over all the items. Values for the food insulin index of the FFQ items were provided by the University of Sydney, Australia. The dietary II was calculated as a function of food insulin index, energy content and consumption frequency of all FFQ items. Multivariate adjusted hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional hazards regression. Results: Between 1986 and 2006, we confirmed 5,112 prostate cancer cases, including 860 advanced/fatal (regionally invasive or metastatic disease at diagnosis, or metastases or death from prostate cancer during follow-up) cases. Dietary GI, GL and II were not associated with risk of total or advanced prostate cancer. For total prostate cancer, the multivariate adjusted HRs comparing the highest versus lowest quintile were 1.01 (CI 0.92-1.12, p-trend=0.26) for GI, 1.07 (CI 0.97-1.19, p-trend=0.19) for GL and 1.05 (CI 0.94-1.17, p-trend=0.15) for II. For advanced prostate cancer, the HRs were 1.05 (CI 0.75-1.47, p-trend=0.76) for GI, 0.99 (CI 0.70-1.40, p-trend=0.64) for GL, and 0.99 (CI 0.68-1.44, p-trend=0.92) for II. Results did not change substantially when the cohort was restricted to men with PSA screening. Stratification by BMI, diabetes and age at diagnosis, or by tumor grade, did not suggest any heterogeneity (all p-values for interaction were >0.11). Conclusion: These results suggest that long-term exposure to a diet with a high insulin response as reflected by high dietary glycemic index, glycemic load and insulin index does not affect prostate cancer incidence or progression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2823.

Abstract 920: Genetic variation in the Toll-like receptor 4 and prostate cancer incidence and mortality

Abstract Background: Several lines of evidence support the roles of inflammation and infection in prostate cancer development and progression. Common genetic variants involved in pathways of inflammation and immune response may be important for prostate cancer. The Toll-like receptor 4 (TLR4) is a cell surface receptor that mediates immune response. TLR4 recognizes LPS (endotoxin) on gram-negative bacteria, resulting in NF-kappaB and cytokine production as well as inducing interferon expression. In vitro studies suggest that stimulation of TLR4 with LPS promotes prostate tumor growth. Yet, single nucleotide polymorphisms (SNPs) on TLR4 have been inconsistently associated with prostate cancer risk, and only one published study has looked at survival as an endpoint. Methods: In a large nested case control study of prostate cancer in the Physicians’ Health Study (1982-2004), 10 SNPs were selected and genotyped to capture common variation within the TLR4 gene as well as 5 kilobases up and downstream. SNPs that were not directly tagged were imputed using the observed genotypes, the HapMap CEPH data, and the MACH imputation program. Unconditional logistic regression controlling for matching factors (age at randomization, smoking status and duration of follow-up) assessed the association of these SNPs and prostate cancer risk (odds ratios (OR) and 95% confidence intervals (CI)), as well as risk defined by advanced cancer stage (T3/T4, T0-T4/M1, fatal disease) or high Gleason grade (>=7). Time to event analysis using Cox-proportional hazards regression assessed risk of progression to metastases and death among prostate cancer cases through March 2009. Results: The case-control analysis included 1286 prostate cancer cases and 1267 controls; there were 237 advanced stage and 560 high grade cases. An additional 45 men who were originally controls developed prostate cancer and were also included in the case-only survival analysis. During a median of 10.6 years of follow-up, 183 men died of prostate cancer or developed distant metastases. No significant associations between the TLR4 SNPs were found for total prostate cancer risk, including SNPs for which an association was reported in other published studies: rs2149356 (OR:0.89, CI: 0.66, 1.18); rs2737191 (OR: 1.01, CI:0.75, 1.37); rs10759932 (OR: 1.08, CI: 0.89, 1.3); rs11536889 (OR: 0.99, CI: 0.83, 1.19). There were no significant associations for risk of advanced stage or high grade cancers, or progression to metastases or death. Conclusions: Results from this prospective nested case-control study, with a large number of aggressive cancers and comprehensive SNP selection on TLR4, suggest that genetic variation across TLR4 is not associated with prostate cancer risk or progression. The results do not replicate the findings of previous studies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 920.

History of diabetes mellitus and the risk of prostate cancer: the Ohsaki Cohort Study

The association between diabetes mellitus and the risk of prostate cancer has been tested in previous prospective cohort studies in western populations. However, no evidence from cohort studies is available for Asian populations, whose lifestyle is very different from that of westerners. The authors examined the relationship between diabetes mellitus and the risk of prostate cancer in the Ohsaki cohort followed from 1995 to 2003, in which 230 new cases of prostate cancer were identified among 22,458 Japanese men. Baseline information including diabetes mellitus status was collected using a self-administered questionnaire. The Cox proportional hazards regression model was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Although a history of diabetes mellitus was not associated with the risk of total prostate cancer in this population, after stratification based on the clinical stage of prostate cancer, patients with diabetes mellitus showed a higher risk of advanced prostate cancer with a multivariate adjusted HR = 1.89 (95% CI: 1.02-3.50). The relationship remained robust when we excluded from the analysis cases arising in the first 2 years. This population-based prospective cohort study indicates that a history of diabetes mellitus is associated with an increased incidence of advanced prostate cancer.

Body size and risk of prostate cancer in Jamaican men

We investigated the associations between body size and risk of prostate cancer in a hospital-based case-control study in Jamaica. Height, weight, waist, and hip circumference were measured at enrollment, and data collected on medical and lifestyle factors for newly diagnosed cases (n = 243) and controls (n = 275). Compared with men in the normal range of waist-hip ratio (WHR), men with WHR > or =0.95 were at greater risk of total prostate cancer (OR,1.72; CI, 1.01-3.00) and high-grade cancer (OR, 2.02; CI, 1.03-3.96). With additional control for BMI, the association with WHR remained significant for total prostate cancer (OR, 1.90; CI, 1.01-3.53) and high-grade disease (OR, 2.94; CI, 1.34-6.38). There was no association between waist circumference and cancer without control for BMI but after controlling for BMI, waist circumference >90 cm (OR, 2.45; CI, 1.01-5.94) and >102 cm (OR, 5.57; CI, 1.43-18.63) showed a dose-response relationship with high-grade disease. Height and BMI were not associated with risk of prostate cancer. Abdominal obesity may be associated with risk of high-grade prostate cancer. Risk may be greater in those with higher abdominal obesity relative to overall size. The results further highlight the importance of investigating relationships by characteristics of the tumor.

Abstract A108: Serum retinol and risk of prostate cancer in the alphatocopherol, beta-carotene (ATBC) cancer prevention study

Abstract Purpose: Retinol (vitamin A) may prevent prostate cancer by promoting cell differentiation and apoptosis, although under some conditions it could stimulate growth and de-differentiation. We examined serum retinol, measured at baseline and three years, in relation to prostate cancer risk in the ATBC Study. Methods: The ATBC Study is a randomized controlled trial conducted to determine the effects of -tocopherol and s-carotene supplements on cancer incidence. 29,133 Finnish male smokers were recruited from 1985–1988 and were assigned to groups using a 2×2 factorial design: 1) -tocopherol, 2) β-scarotene, 3) both supplements, or 4) placebo. Fasting blood samples were collected at baseline and after 3 years, and as of April 30, 2006, 2,041 prostate cancer cases occurred during 417,532 person-years. Cox proportional hazards models were used to estimate the relative risk (as hazard ratio, HR) of total and aggressive (n=461) prostate cancer by quintile of baseline and 3-year serum retinol concentrations, as well as by change in serum retinol. No confounding by factors associated with either prostate cancer or retinol was observed. Results: Men in higher quintiles of baseline retinol were more likely to develop prostate cancer compared with men in the lowest quintile (age-adjusted HR, 95%CI vs. Q1; Q2: 1.05, 0.91 – 1.21; Q3: 1.06 0.92 – 1.22; Q4: 1.13, 0.98 – 1.30; Q5: 1.19, 1.03 – 1.36; p-trend = 0.009). The association was similar for aggressive prostate cancer and when the 3-year retinol was used. Compared to men whose retinol did not differ between baseline and 3 years, men with either higher or lower retinol at follow-up were at similar risk of prostate cancer. When we jointly categorized men based on quintiles of baseline and 3-year retinol, we noted that men who were in the highest quintile of retinol at both time points had the greatest increased risk (baseline/3-year Q5/Q5 vs. Q1/Q1 HR: 1.31 95% CI: 1.08 – 1.59). Other joint categories were also at higher risk, particularly among men who did not receive the trial β-carotene supplement. Men randomized to the β-carotene arm had generally higher risk for any baseline/3-year retinol category compared to men in the no β-carotene arm, and those whose serum retinol decreased substantially from baseline Q4 or Q5 appeared to have a lower prostate cancer risk (HR, 95% CI vs. Q1/Q1; Q5 to Q1–3: 0.60, 0.35 – 1.03; Q4 to Q1–2: 0.85, 0.54 – 1.33). Conclusion: In this largest study to date of serum retinol and prostate cancer that incorporates retinol measured at two time points three years apart, higher serum concentrations were associated with elevated risk, with sustained high exposure conferring the greatest risk. Distinct patterns of change in serum retinol over time may relate to differing risks of developing prostate cancer. Citation Information: Cancer Prev Res 2010;3(1 Suppl):A108.

Abstract A106: Coffee consumption and risk of lethal and advanced prostate cancer

Abstract Background: Coffee is a commonly consumed beverage which contains many biologically active compounds. It is a major source of caffeine and antioxidants, and it has effects on insulin and glucose metabolism as well as sex hormone levels. This suggests that coffee may have a beneficial effect on risk of prostate cancer; however, this association has not been studied in depth. Methods: We prospectively investigated the association between coffee intake and prostate cancer risk in the Health Professionals' Follow-Up Study. From 1986 to 2006, 4975 cases of prostate cancer were identified. Intake of regular and decaffeinated coffee was assessed in 1986 and every four years thereafter. We used Cox proportional hazards models to assess the association between coffee intake and risk of prostate cancer. To investigate possible mechanisms, we used linear regression to examine the cross-sectional association between coffee intake and levels of circulating hormones in blood samples collected between 1993 and 1995 from a subset of men in the cohort. Results: There was a weak inverse association between total coffee intake and overall prostate cancer risk, with an adjusted relative risk of 0.81 (95% CI: 0.67–0.97, p-value for linear trend=0.08) for men consuming six or more cups of coffee (regular or decaf) per day compared to non-drinkers. The association was stronger for lethal and advanced (fatal, T3b or T4, or N1 or M1) prostate cancers. Compared to non-drinkers, the highest consumers had a relative risk of 0.41 (CI: 0.22–0.77, p-trend=0.02) for lethal cancer and 0.41 (CI: 0.24–0.71, p-trend=0.002) for advanced cancer. The association with lethal and advanced cancers was more pronounced in never smoking men (RR=0.11; CI: 0.02–0.83, p-trend=0.001 for advanced cancer). The inverse association was seen in both the pre-PSA and PSA screening eras. Results were similar for regular and decaffeinated coffee. For the highest versus lowest groups of intake, the relative risk of advanced cancer was 0.67 (CI: 0.34–1.33, p-trend=0.03) for regular coffee and 0.72 (CI: 0.46–1.13, p-trend=0.03) for decaffeinated coffee. There was an inverse association between caffeine intake and risk of lethal and advanced disease, but this association was weaker than that seen for coffee, and it became non-significant when total coffee intake was also included in the model. Coffee intake was inversely associated with plasma levels of C-peptide (p-trend=0.003) and positively associated with testosterone (p-trend=0.03) and SHBG (p-trend=0.04). Coffee intake was not related to circulating levels of IGF-1, IGFBP3, free testosterone, or estradiol. Conclusion: The strong inverse association between coffee consumption and risk of lethal and advanced prostate cancers is potentially important and should be confirmed in other populations. The association appears to be related to non-caffeine components of coffee and may be mediated through effects on insulin metabolism and/or sex hormone levels. Citation Information: Cancer Prev Res 2010;3(1 Suppl):A106.

Fruits and Vegetables in Relation to Prostate Cancer in Japanese Men: The Japan Public Health Center-Based Prospective Study

Although dietary risk factors may differ between localized and advanced prostate cancer, data on associations between the consumption of fruits and vegetables and risk of localized and advanced cancers are limited. We examined associations between fruit and vegetable consumption and risk of prostate cancer in a Japanese population. During 1995–1998, a validated food frequency questionnaire was administered to 43,475 men aged 45–74 yr. During 321,061 person-years of follow-up until the end of 2004, 339 cases of prostate cancer were identified. Consumption of fruits or total vegetables was not associated with a decreased risk of total prostate cancer, with corresponding multivariate hazard ratios of the highest vs. lowest quartiles of 1.09 (95% CI = 0.77–1.53; trend P = 0.39) for fruits and 1.33 (95% CI = 0.93–1.91; trend P = 0.52) for total vegetables. Also, no association was observed for intake of either fruits or vegetables (total or any subtype) with localized or advanced prostate cancer. This prospective cohort study suggests that consumption of fruits or vegetables may not be associated with the risk of either localized or advanced prostate cancer in Japanese men. However, the possibility of confounding by detection bias on the risk of localized cancer could not be totally ruled out.

A prospective study of lifetime physical activity and prostate cancer incidence and mortality

Background:The possible benefit of lifetime physical activity (PA) in reducing prostate cancer incidence and mortality is unclear.Methods:A prospective cohort of 45 887 men aged 45–79 years was followed up from January 1998 to December 2007 for prostate cancer incidence (n=2735) and to December 2006 for its subtypes and for fatal (n=190) prostate cancer.Results:We observed an inverse association between lifetime (average of age 30 and 50 years, and baseline age) total PA levels and prostate cancer risk. Multivariate-adjusted incidence in the top quartile of lifetime total PA decreased by 16% (95% confidence interval (CI)=2–27%) compared with that in the bottom quartile. We also observed an inverse association between average lifetime work or occupational activity and walking or bicycling duration and prostate cancer risk. Compared with men who mostly sit during their main work or occupation, men who sit half of the time experienced a 20% lower risk (95% CI=7–31%). The rate ratio linearly decreased by 7% (95% CI=1–12%) for total, 8% (95% CI=0–16%) for localised and 12% (95% CI=2–20%) for advanced prostate cancer for every 30 min per day increment of lifetime walking or bicycling in the range of 30 to 120 min per day.Conclusions:Our results suggest that not sitting for most of the time during work or occupational activity and walking or bicycling more than 30 min per day during adult life is associated with reduced incidence of prostate cancer.

Dietary Supplement Use and Prostate Cancer Risk in the Carotene and Retinol Efficacy Trial

We investigated dietary supplement use and prostate cancer risk in the Carotene and Retinol Efficacy Trial (CARET). CARET was a randomized, double-blinded, placebo-controlled trial testing a daily dose of 30 mg beta-carotene + 25,000 IU retinyl palmitate for lung cancer prevention (1985-1996; active follow-up occurred through 2005). Secondary outcomes, including prostate cancer, were also assessed. Participants were queried about dietary supplements, health history, family history of cancer, smoking, and lifestyle habits. Cox proportional hazards regression estimated multivariate-adjusted relative risk [and 95% confidence intervals (95% CI)] of prostate cancer for dietary supplement users and nonusers with or without the high-dose CARET vitamins during the intervention and postintervention phases. After an average of 11 years of follow-up, 890 prostate cancer cases were reported. Neither the CARET nor other supplements were associated with total prostate cancer risk. For aggressive prostate cancer, men in the CARET intervention arm who used additional supplements had a relative risk for aggressive prostate cancer (Gleason >or=7 or stage III/IV) of 1.52 (95% CI, 1.03-2.24; P < 0.05), relative to all others. These associations disappeared in the postintervention period (0.75; 95% CI, 0.51-1.09). Conversely, there was no association of CARET + other supplements with nonaggressive disease, relative to all others. There was no effect modification by smoking or time on CARET intervention in any analyses. CARET only included smokers, so findings reported here may not apply to nonsmokers. Our results are consistent with other studies suggesting that dietary supplements may influence prostate cancer risk.

Alcohol consumption, finasteride, and prostate cancer risk: results from the Prostate Cancer Prevention Trial.

Current research is inconclusive regarding the relation between alcohol consumption and prostate cancer risk. In this study, the authors examined the associations of total alcohol, type of alcoholic beverage, and drinking pattern with the risk of total, low-grade, and high-grade prostate cancer. Data for this study came from the 2129 participants in the Prostate Cancer Prevention Trial (PCPT) who had cancer detected during the 7-year trial and 8791 men who were determined by biopsy to be free of cancer at the trial end. Poisson regression was used to calculate relative risks (RRs) and 95% confidence intervals (95% CIs) for associations of alcohol intake with prostate cancer risk. Associations of drinking with high-grade disease did not differ by treatment arm. In combined arms, heavy alcohol consumption (> or =50 g of alcohol daily) and regular heavy drinking (> or =4 drinks daily on > or =5 days per week) were associated with increased risks of high-grade prostate cancer (RR, 2.01 [95% CI, 1.33-3.05] and 2.17 [95% CI, 1.42-3.30], respectively); less heavy drinking was not associated with risk. Associations of drinking with low-grade cancer differed by treatment arm. In the placebo arm, there was no association of drinking with risk of low-grade cancer. In the finasteride arm, drinking > or =50 g of alcohol daily was associated with an increased risk of low-grade disease (RR, 1.89; 95% CI, 1.39-2.56); this finding was because of a 43% reduction in the risk of low-grade cancer attributable to finasteride treatment in men who drank <50 g of alcohol daily and the lack of an effect of finasteride in men who drank > or =50 g of alcohol daily (P(interaction) = .03). Heavy, daily drinking increased the risk of high-grade prostate cancer. Heavy drinking made finasteride ineffective for reducing prostate cancer risk.

C-reactive protein haplotype is associated with high PSA as a marker of metastatic prostate cancer but not with overall cancer risk

Growing evidence points to a role for inflammation in prostate carcinogenesis. The significance of C-reactive protein (CRP), an inflammatory and innate immunity molecule, has not been evaluated thoroughly in prostate cancer (PC). In this study of 739 Finnish patients with PC and 760 healthy men, we evaluated the associations of CRP genotypes and haplotypes with total PC risk and PC progression, using prostate-specific antigen (PSA) as a marker of metastatic disease. Although the haplotype frequencies were similar in patients and controls, an association between haplotype ACCCA and patients' PSA levels was found. The carriers more often had a high PSA than non-carriers (P=0.0002) and the SNP rs2794521 A-allele and rs1800947 C-allele carriers had a higher PSA than non-carriers (P=0.009 and P=0.0004, respectively). A trend for a younger age at diagnosis was found among the carriers of ACCCA (P=0.07) and the rs1800947 C-allele (P=0.06), as well as a trend for the latter to have more likely metastases (P=0.06), but not after Bonferroni correction (α=0.00208). This is the first study to suggest association between PSA and CRP variants in PC and, therefore, further studies are warranted. CRP alleles previously found to protect against increased CRP levels are now suggested to be associated with metastatic PC, indicated by elevated PSA.

Plasma Isoflavones and Subsequent Risk of Prostate Cancer in a Nested Case-Control Study: The Japan Public Health Center

The incidence of prostate cancer is much lower in Japanese than Western populations. Given the preventive effects of isoflavones on carcinogenesis in the prostate in many nonhuman studies and the high consumption of isoflavones in Japanese, this low incidence may be partly due to the effects of soy. We conducted a nested case-control study within the Japan Public Health Center-based Prospective Study. A total of 14,203 men aged 40 to 69 years who had returned the baseline questionnaire and provided blood samples were observed from 1990 to 2005. During a mean of 12.8 years of follow-up, 201 newly diagnosed prostate cancers were identified. Two matched controls for each case were selected from the cohort. Conditional logistic regression model was used to estimate the odds ratios (ORs) and 95% CIs for prostate cancer in relation to plasma levels of isoflavone. Plasma genistein level tended to be inversely associated with the risk of total prostate cancer. Although plasma daidzein showed no association, the highest tertile for plasma equol, a metabolite of daidzein, was significantly associated with a decreased risk of total prostate cancer (OR = 0.60; 95% CI, 0.36 to 0.99; P(trend) = .04). These inverse associations were strengthened after analysis was confined to localized cases, with ORs in the highest group of plasma genistein and equol compared with the lowest of 0.54 (95% CI, 0.29 to 1.01; P(trend) = .03) and 0.43 (95% CI, 0.22 to 0.82; P(trend) = .02), respectively. Plasma isoflavone levels were not statistically significantly associated with the risk of advanced prostate cancer. Isoflavones may prevent the development of prostate cancer.

Fatty acid composition of plasma phospholipids and risk of prostate cancer in a case-control analysis nested within the European Prospective Investigation into Cancer and Nutrition

Background:Plausible biological mechanisms underlie possible associations between fatty acids in blood and risk of prostate cancer; epidemiologic evidence for an association, however, is inconsistent. Objective:The objectives were to assess the association between plasma phospholipid fatty acids and risk of total prostate cancer by stage and grade. Design:This was a nested case-control analysis of 962 men with a diagnosis of prostate cancer after a median follow-up time of 4.2 y and 1061 matched controls who were taking part in the European Prospective Investigation into Cancer and Nutrition. The fatty acid composition of plasma phospholipids was measured by gas chromatography, and the risk of prostate cancer was estimated by using conditional logistic regression with adjustment for lifestyle variables. Results:We found a positive association between palmitic acid and risk of total, localized, and low-grade prostate cancer. The risk of prostate cancer for men in the highest quintile compared with the lowest quintile of palmitic acid was 1.47 (95% CI: 0.97, 2.23; P for trend = 0.032). We found an inverse association between stearic acid and the risk of total, localized, and low-grade prostate cancer; men in the highest quintile of stearic acid had a relative risk of 0.77 (95% CI: 0.56, 1.06; P for trend = 0.03). There were significant positive associations between myristic, α-linolenic, and eicosapentaenoic acids and risk of high-grade prostate cancer. Conclusion:The associations between palmitic, stearic, myristic, α-linolenic, and eicosapentaenoic acids and prostate cancer risk may reflect differences in intake or metabolism of these fatty acids between the precancer cases and controls and should be explored further.