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Metabolomics may reveal novel insights into the etiology of prostate cancer, for which few risk factors are established. We investigated the association between patterns in baseline plasma metabolite profile and subsequent prostate cancer risk, using data from 3,057 matched case-control sets from the European Prospective Investigation into Cancer and Nutrition (EPIC). We measured 119 metabolite concentrations in plasma samples, collected on average 9.4 years before diagnosis, by mass spectrometry (AbsoluteIDQ p180 Kit, Biocrates Life Sciences AG). Metabolite patterns were identified using treelet transform, a statistical method for identification of groups of correlated metabolites. Associations of metabolite patterns with prostate cancer risk (OR 1SD ) were estimated by conditional logistic regression. Supplementary analyses were conducted for metabolite patterns derived using principal component analysis and for individual metabolites. Men with metabolite profiles characterized by higher concentrations of either phosphatidylcholines or hydroxysphingomyelins (OR 1SD  = 0.77, 95% confidence interval 0.66-0.89), acylcarnitines C18:1 and C18:2, glutamate, ornithine and taurine (OR 1SD  = 0.72, 0.57-0.90), or lysophosphatidylcholines (OR 1SD  = 0.81, 0.69-0.95) had lower risk of advanced stage prostate cancer at diagnosis, with no evidence of heterogeneity by follow-up time. Similar associations were observed for the two former patterns with aggressive disease risk (the more aggressive subset of advanced stage), while the latter pattern was inversely related to risk of prostate cancer death (OR 1SD  = 0.77, 0.61-0.96). No associations were observed for prostate cancer overall or less aggressive tumor subtypes. In conclusion, metabolite patterns may be related to lower risk of more aggressive prostate tumors and prostate cancer death, and might be relevant to etiology of advanced stage prostate cancer., (© 2019 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

The associations of individual dietary fatty acids with prostate cancer risk have not been examined comprehensively. We examined the prospective association of individual dietary fatty acids with prostate cancer risk overall, by tumor subtypes, and prostate cancer death. 142,239 men from the European Prospective Investigation into Cancer and Nutrition who were free from cancer at recruitment were included. Dietary intakes of individual fatty acids were estimated using center-specific validated dietary questionnaires at baseline and calibrated with 24-h recalls. Multivariable Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). After an average follow-up of 13.9 years, 7,036 prostate cancer cases and 936 prostate cancer deaths were ascertained. Intakes of individual fatty acids were not related to overall prostate cancer risk. There was evidence of heterogeneity in the association of some short chain saturated fatty acids with prostate cancer risk by tumor stage (p heterogeneity < 0.015), with a positive association with risk of advanced stage disease for butyric acid (4:0; HR 1SD = 1.08; 95%CI = 1.01-1.15; p-trend = 0.026). There were no associations with fatal prostate cancer, with the exception of a slightly higher risk for those who consumed more eicosenoic acid (22:1n-9c; HR 1SD = 1.05; 1.00-1.11; p-trend = 0.048) and eicosapentaenoic acid (20:5n-3c; HR 1SD = 1.07; 1.00-1.14; p-trend = 0.045). There was no evidence that dietary intakes of individual fatty acids were associated with overall prostate cancer risk. However, a higher intake of butyric acid might be associated with a higher risk of advanced, whereas intakes of eicosenoic and eicosapentaenoic acids might be positively associated with fatal prostate cancer risk., (© 2019 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Previous prospective studies assessing the relationship between circulating concentrations of vitamin D and prostate cancer risk have shown inconclusive results, particularly for risk of aggressive disease. In this study, we examine the association between prediagnostic concentrations of 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH) 2 D] and the risk of prostate cancer overall and by tumor characteristics. Principal investigators of 19 prospective studies provided individual participant data on circulating 25(OH)D and 1,25(OH) 2 D for up to 13,462 men with incident prostate cancer and 20,261 control participants. ORs for prostate cancer by study-specific fifths of season-standardized vitamin D concentration were estimated using multivariable-adjusted conditional logistic regression. 25(OH)D concentration was positively associated with risk for total prostate cancer (multivariable-adjusted OR comparing highest vs. lowest study-specific fifth was 1.22; 95% confidence interval, 1.13-1.31; P trend < 0.001). However, this association varied by disease aggressiveness ( P heterogeneity = 0.014); higher circulating 25(OH)D was associated with a higher risk of nonaggressive disease (OR per 80 percentile increase = 1.24, 1.13-1.36) but not with aggressive disease (defined as stage 4, metastases, or prostate cancer death, 0.95, 0.78-1.15). 1,25(OH) 2 D concentration was not associated with risk for prostate cancer overall or by tumor characteristics. The absence of an association of vitamin D with aggressive disease does not support the hypothesis that vitamin D deficiency increases prostate cancer risk. Rather, the association of high circulating 25(OH)D concentration with a higher risk of nonaggressive prostate cancer may be influenced by detection bias. SIGNIFICANCE: This international collaboration comprises the largest prospective study on blood vitamin D and prostate cancer risk and shows no association with aggressive disease but some evidence of a higher risk of nonaggressive disease., (©2018 American Association for Cancer Research.)

Phytoestrogens may influence prostate cancer development. This study aimed to examine the association between prediagnostic circulating concentrations of isoflavones (genistein, daidzein, equol) and lignans (enterolactone and enterodiol) and the risk of prostate cancer. Individual participant data were available from seven prospective studies (two studies from Japan with 241 cases and 503 controls and five studies from Europe with 2,828 cases and 5,593 controls). Because of the large difference in circulating isoflavone concentrations between Japan and Europe, analyses of the associations of isoflavone concentrations and prostate cancer risk were evaluated separately. Prostate cancer risk by study-specific fourths of circulating concentrations of each phytoestrogen was estimated using multivariable-adjusted conditional logistic regression. In men from Japan, those with high compared to low circulating equol concentrations had a lower risk of prostate cancer (multivariable-adjusted OR for upper quartile [Q4] vs. Q1 = 0.61, 95% confidence interval [CI] = 0.39-0.97), although there was no significant trend (OR per 75 percentile increase = 0.69, 95 CI = 0.46-1.05, p trend = 0.085); Genistein and daidzein concentrations were not significantly associated with risk (ORs for Q4 vs. Q1 = 0.70, 0.45-1.10 and 0.71, 0.45-1.12, respectively). In men from Europe, circulating concentrations of genistein, daidzein and equol were not associated with risk. Circulating lignan concentrations were not associated with the risk of prostate cancer, overall or by disease aggressiveness or time to diagnosis. There was no strong evidence that prediagnostic circulating concentrations of isoflavones or lignans are associated with prostate cancer risk, although further research is warranted in populations where isoflavone intakes are high., (© 2018 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Background: Experimental and clinical evidence implicates testosterone in the aetiology of prostate cancer. Variation across the normal range of circulating free testosterone concentrations may not lead to changes in prostate biology, unless circulating concentrations are low. This may also apply to prostate cancer risk, but this has not been investigated in an epidemiological setting., Objective: To examine whether men with low concentrations of circulating free testosterone have a reduced risk of prostate cancer., Design, Setting, and Participants: Analysis of individual participant data from 20 prospective studies including 6933 prostate cancer cases, diagnosed on average 6.8 yr after blood collection, and 12 088 controls in the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group., Outcome Measurements and Statistical Analysis: Odds ratios (ORs) of incident overall prostate cancer and subtypes by stage and grade, using conditional logistic regression, based on study-specific tenths of calculated free testosterone concentration., Results and Limitations: Men in the lowest tenth of free testosterone concentration had a lower risk of overall prostate cancer (OR=0.77, 95% confidence interval [CI] 0.69-0.86; p<0.001) compared with men with higher concentrations (2nd-10th tenths of the distribution). Heterogeneity was present by tumour grade (p het =0.01), with a lower risk of low-grade disease (OR=0.76, 95% CI 0.67-0.88) and a nonsignificantly higher risk of high-grade disease (OR=1.56, 95% CI 0.95-2.57). There was no evidence of heterogeneity by tumour stage. The observational design is a limitation., Conclusions: Men with low circulating free testosterone may have a lower risk of overall prostate cancer; this may be due to a direct biological effect, or detection bias. Further research is needed to explore the apparent differential association by tumour grade., Patient Summary: In this study, we looked at circulating testosterone levels and risk of developing prostate cancer, finding that men with low testosterone had a lower risk of prostate cancer., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Several dietary factors have been studied in relation to prostate cancer; however, most studies have not reported on subtypes of fruit and vegetables or tumor characteristics, and results obtained so far are inconclusive. This study aimed to examine the prospective association of total and subtypes of fruit and vegetable intake with the incidence of prostate cancer overall, by grade and stage of disease, and prostate cancer death. Lifestyle information for 142,239 men participating in the European Prospective Investigation into Cancer and Nutrition from 8 European countries was collected at baseline. Multivariable Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). After an average follow-up time of 13.9 years, 7,036 prostate cancer cases were identified. Compared with the lowest fifth, those in the highest fifth of total fruit intake had a significantly reduced prostate cancer risk (HR = 0.91; 95% CI = 0.83-0.99; p-trend = 0.01). No associations between fruit subtypes and prostate cancer risk were observed, except for citrus fruits, where a significant trend was found (HR = 0.94; 95% CI = 0.86-1.02; p-trend = 0.01). No associations between total and subtypes of vegetables and prostate cancer risk were observed. We found no evidence of heterogeneity in these associations by tumor grade and stage, with the exception of significant heterogeneity by tumor grade (p heterogeneity <0.001) for leafy vegetables. No significant associations with prostate cancer death were observed. The main finding of this prospective study was that a higher fruit intake was associated with a small reduction in prostate cancer risk. Whether this association is causal remains unclear., (© 2017 The Authors International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Background: The relationship between body size and prostate cancer risk, and in particular risk by tumour characteristics, is not clear because most studies have not differentiated between high-grade or advanced stage tumours, but rather have assessed risk with a combined category of aggressive disease. We investigated the association of height and adiposity with incidence of and death from prostate cancer in 141,896 men in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort., Methods: Multivariable-adjusted Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). After an average of 13.9 years of follow-up, there were 7024 incident prostate cancers and 934 prostate cancer deaths., Results: Height was not associated with total prostate cancer risk. Subgroup analyses showed heterogeneity in the association with height by tumour grade (P heterogeneity  = 0.002), with a positive association with risk for high-grade but not low-intermediate-grade disease (HR for high-grade disease tallest versus shortest fifth of height, 1.54; 95% CI, 1.18-2.03). Greater height was also associated with a higher risk for prostate cancer death (HR = 1.43, 1.14-1.80). Body mass index (BMI) was significantly inversely associated with total prostate cancer, but there was evidence of heterogeneity by tumour grade (P heterogeneity  = 0.01; HR = 0.89, 0.79-0.99 for low-intermediate grade and HR = 1.32, 1.01-1.72 for high-grade prostate cancer) and stage (P heterogeneity  = 0.01; HR = 0.86, 0.75-0.99 for localised stage and HR = 1.11, 0.92-1.33 for advanced stage). BMI was positively associated with prostate cancer death (HR = 1.35, 1.09-1.68). The results for waist circumference were generally similar to those for BMI, but the associations were slightly stronger for high-grade (HR = 1.43, 1.07-1.92) and fatal prostate cancer (HR = 1.55, 1.23-1.96)., Conclusions: The findings from this large prospective study show that men who are taller and who have greater adiposity have an elevated risk of high-grade prostate cancer and prostate cancer death.

Background: Little is known about how pre-diagnostic metabolites in blood relate to risk of prostate cancer. We aimed to investigate the prospective association between plasma metabolite concentrations and risk of prostate cancer overall, and by time to diagnosis and tumour characteristics, and risk of death from prostate cancer., Methods: In a case-control study nested in the European Prospective Investigation into Cancer and Nutrition, pre-diagnostic plasma concentrations of 122 metabolites (including acylcarnitines, amino acids, biogenic amines, glycerophospholipids, hexose and sphingolipids) were measured using targeted mass spectrometry (AbsoluteIDQ p180 Kit) and compared between 1077 prostate cancer cases and 1077 matched controls. Risk of prostate cancer associated with metabolite concentrations was estimated by multi-variable conditional logistic regression, and multiple testing was accounted for by using a false discovery rate controlling procedure., Results: Seven metabolite concentrations, i.e. acylcarnitine C18:1, amino acids citrulline and trans-4-hydroxyproline, glycerophospholipids PC aa C28:1, PC ae C30:0 and PC ae C30:2, and sphingolipid SM (OH) C14:1, were associated with prostate cancer (p < 0.05), but none of the associations were statistically significant after controlling for multiple testing. Citrulline was associated with a decreased risk of prostate cancer (odds ratio (OR 1SD ) = 0.73; 95% confidence interval (CI) 0.62-0.86; p trend  = 0.0002) in the first 5 years of follow-up after taking multiple testing into account, but not after longer follow-up; results for other metabolites did not vary by time to diagnosis. After controlling for multiple testing, 12 glycerophospholipids were inversely associated with advanced stage disease, with risk reduction up to 46% per standard deviation increase in concentration (OR 1SD  = 0.54; 95% CI 0.40-0.72; p trend  = 0.00004 for PC aa C40:3). Death from prostate cancer was associated with higher concentrations of acylcarnitine C3, amino acids methionine and trans-4-hydroxyproline, biogenic amine ADMA, hexose and sphingolipid SM (OH) C14:1 and lower concentration of glycerophospholipid PC aa C42:4., Conclusions: Several metabolites, i.e. C18:1, citrulline, trans-4-hydroxyproline, three glycerophospholipids and SM (OH) C14:1, might be related to prostate cancer. Analyses by time to diagnosis indicated that citrulline may be a marker of subclinical prostate cancer, while other metabolites might be related to aetiology. Several glycerophospholipids were inversely related to advanced stage disease. More prospective data are needed to confirm these associations.

Background: Folate and vitamin B 12 are essential for maintaining DNA integrity and may influence prostate cancer (PCa) risk, but the association with clinically relevant, advanced stage, and high-grade disease is unclear., Objective: To investigate the associations between circulating folate and vitamin B 12 concentrations and risk of PCa overall and by disease stage and grade., Design, Setting, and Participants: A study was performed with a nested case-control design based on individual participant data from six cohort studies including 6875 cases and 8104 controls; blood collection from 1981 to 2008, and an average follow-up of 8.9 yr (standard deviation 7.3). Odds ratios (ORs) of incident PCa by study-specific fifths of circulating folate and vitamin B 12 were calculated using multivariable adjusted conditional logistic regression., Outcome Measurements and Statistical Analysis: Incident PCa and subtype by stage and grade., Results and Limitations: Higher folate and vitamin B 12 concentrations were associated with a small increase in risk of PCa (ORs for the top vs bottom fifths were 1.13 [95% confidence interval (CI), 1.02-1.26], p trend =0.018, for folate and 1.12 [95% CI, 1.01-1.25], p trend =0.017, for vitamin B 12 ), with no evidence of heterogeneity between studies. The association with folate varied by tumour grade (p heterogeneity <0.001); higher folate concentration was associated with an elevated risk of high-grade disease (OR for the top vs bottom fifth: 2.30 [95% CI, 1.28-4.12]; p trend =0.001), with no association for low-grade disease. There was no evidence of heterogeneity in the association of folate with risk by stage or of vitamin B 12 with risk by stage or grade of disease (p heterogeneity >0.05). Use of single blood-sample measurements of folate and B 12 concentrations is a limitation., Conclusions: The association between higher folate concentration and risk of high-grade disease, not evident for low-grade disease, suggests a possible role for folate in the progression of clinically relevant PCa and warrants further investigation., Patient Summary: Folate, a vitamin obtained from foods and supplements, is important for maintaining cell health. In this study, however, men with higher blood folate levels were at greater risk of high-grade (more aggressive) prostate cancer compared with men with lower folate levels. Further research is needed to investigate the possible role of folate in the progression of this disease., (Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Some observational studies suggest that a higher selenium status is associated with a lower risk of prostate cancer but have been generally too small to provide precise estimates of associations, particularly by disease stage and grade., Methods: Collaborating investigators from 15 prospective studies provided individual-participant records (from predominantly men of white European ancestry) on blood or toenail selenium concentrations and prostate cancer risk. Odds ratios of prostate cancer by selenium concentration were estimated using multivariable-adjusted conditional logistic regression. All statistical tests were two-sided., Results: Blood selenium was not associated with the risk of total prostate cancer (multivariable-adjusted odds ratio [OR] per 80 percentile increase = 1.01, 95% confidence interval [CI] = 0.83 to 1.23, based on 4527 case patients and 6021 control subjects). However, there was heterogeneity by disease aggressiveness (ie, advanced stage and/or prostate cancer death, Pheterogeneity = .01), with high blood selenium associated with a lower risk of aggressive disease (OR = 0.43, 95% CI = 0.21 to 0.87) but not with nonaggressive disease. Nail selenium was inversely associated with total prostate cancer (OR = 0.29, 95% CI = 0.22 to 0.40, Ptrend < .001, based on 1970 case patients and 2086 control subjects), including both nonaggressive (OR = 0.33, 95% CI = 0.22 to 0.50) and aggressive disease (OR = 0.18, 95% CI = 0.11 to 0.31, Pheterogeneity = .08)., Conclusions: Nail, but not blood, selenium concentration is inversely associated with risk of total prostate cancer, possibly because nails are a more reliable marker of long-term selenium exposure. Both blood and nail selenium concentrations are associated with a reduced risk of aggressive disease, which warrants further investigation., (© The Author 2016. Published by Oxford University Press.)

The role of insulin-like growth factors (IGF) in prostate cancer development is not fully understood. To investigate the association between circulating concentrations of IGFs (IGF-I, IGF-II, IGFBP-1, IGFBP-2, and IGFBP-3) and prostate cancer risk, we pooled individual participant data from 17 prospective and two cross-sectional studies, including up to 10,554 prostate cancer cases and 13,618 control participants. Conditional logistic regression was used to estimate the ORs for prostate cancer based on the study-specific fifth of each analyte. Overall, IGF-I, IGF-II, IGFBP-2, and IGFBP-3 concentrations were positively associated with prostate cancer risk (Ptrend all ≤ 0.005), and IGFBP-1 was inversely associated weakly with risk (Ptrend = 0.05). However, heterogeneity between the prospective and cross-sectional studies was evident (Pheterogeneity = 0.03), unless the analyses were restricted to prospective studies (with the exception of IGF-II, Pheterogeneity = 0.02). For prospective studies, the OR for men in the highest versus the lowest fifth of each analyte was 1.29 (95% confidence interval, 1.16-1.43) for IGF-I, 0.81 (0.68-0.96) for IGFBP-1, and 1.25 (1.12-1.40) for IGFBP-3. These associations did not differ significantly by time-to-diagnosis or tumor stage or grade. After mutual adjustment for each of the other analytes, only IGF-I remained associated with risk. Our collaborative study represents the largest pooled analysis of the relationship between prostate cancer risk and circulating concentrations of IGF-I, providing strong evidence that IGF-I is highly likely to be involved in prostate cancer development. Cancer Res; 76(8); 2288-300. ©2016 AACR., (©2016 American Association for Cancer Research.)

Background: Individual studies have suggested that circulating carotenoids, retinol, or tocopherols may be associated with prostate cancer risk, but the studies have not been large enough to provide precise estimates of associations, particularly by stage and grade of disease., Objective: The objective of this study was to conduct a pooled analysis of the associations of the concentrations of 7 carotenoids, retinol, α-tocopherol, and γ-tocopherol with risk of prostate cancer and to describe whether any associations differ by stage or grade of the disease or other factors., Design: Principal investigators of prospective studies provided individual participant data for prostate cancer cases and controls. Risk by study-specific fifths of each biomarker was estimated by using multivariable-adjusted conditional logistic regression in matched case-control sets., Results: Data were available for up to 11,239 cases (including 1654 advanced stage and 1741 aggressive) and 18,541 controls from 15 studies. Lycopene was not associated with overall risk of prostate cancer, but there was statistically significant heterogeneity by stage of disease, and the OR for aggressive disease for the highest compared with the lowest fifth of lycopene was 0.65 (95% CI: 0.46, 0.91; P-trend = 0.032). No other carotenoid was significantly associated with overall risk of prostate cancer or with risk of advanced-stage or aggressive disease. For retinol, the OR for the highest compared with the lowest fifth was 1.13 (95% CI: 1.04, 1.22; P-trend = 0.015). For α-tocopherol, the OR for the highest compared with the lowest fifth was 0.86 (95% CI: 0.78, 0.94; P-trend < 0.001), with significant heterogeneity by stage of disease; the OR for aggressive prostate cancer was 0.74 (95% CI: 0.59, 0.92; P-trend = 0.001). γ-Tocopherol was not associated with risk., Conclusions: Overall prostate cancer risk was positively associated with retinol and inversely associated with α-tocopherol, and risk of aggressive prostate cancer was inversely associated with lycopene and α-tocopherol. Whether these associations reflect causal relations is unclear., (© 2015 American Society for Nutrition.)

The current epidemiologic evidence suggests that men with type 2 diabetes mellitus may be at lower risk of developing prostate cancer, but little is known about its association with stage and grade of the disease. The association between self-reported diabetes mellitus at recruitment and risk of prostate cancer was examined in the European Prospective Investigation into Cancer and Nutrition (EPIC). Among 139,131 eligible men, 4,531 were diagnosed with prostate cancer over an average follow-up of 12 years. Multivariable hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional hazards models stratified by EPIC-participating center and age at recruitment, and adjusted for education, smoking status, body mass index, waist circumference, and physical activity. In a subset of men without prostate cancer, the cross-sectional association between circulating concentrations of androgens and insulin-like growth factor proteins with diabetes status was also investigated using linear regression models. Compared to men with no diabetes, men with diabetes had a 26% lower risk of prostate cancer (HR, 0.74; 95% CI, 0.63-0.86). There was no evidence that the association differed by stage (p-heterogeneity, 0.19) or grade (p-heterogeneity, 0.48) of the disease, although the numbers were small in some disease subgroups. In a subset of 626 men with hormone measurements, circulating concentrations of androstenedione, total testosterone and insulin-like growth factor binding protein-three were lower in men with diabetes compared to men without diabetes. This large European study has confirmed an inverse association between self-reported diabetes mellitus and subsequent risk of prostate cancer., (© 2014 UICC.)

Background: Individual studies have suggested that some circulating fatty acids are associated with prostate cancer risk, but have not been large enough to provide precise estimates of associations, particularly by stage and grade of disease., Methods: Principal investigators of prospective studies on circulating fatty acids and prostate cancer were invited to collaborate. Investigators provided individual participant data on circulating fatty acids (weight percent) and other characteristics of prostate cancer cases and controls. Prostate cancer risk by study-specific fifths of 14 fatty acids was estimated using multivariable-adjusted conditional logistic regression. All statistical tests were two-sided., Results: Five thousand and ninety-eight case patients and 6649 control patients from seven studies with an average follow-up of 5.1 (SD = 3.3) years were included. Stearic acid (18:0) was inversely associated with total prostate cancer (odds ratio [OR] Q5 vs Q1 = 0.88, 95% confidence interval [CI] = 0.78 to 1.00, P trend = .043). Prostate cancer risk was, respectively, 14% and 16% greater in the highest fifth of eicosapentaenoic acid (20:5n-3) (OR = 1.14, 95% CI = 1.01 to 1.29, Ptrend = .001) and docosapentaenoic acid (22:5n-3) (OR = 1.16, 95% CI = 1.02 to 1.33, P trend = .003), but in each case there was heterogeneity between studies (P = .022 and P < .001, respectively). There was heterogeneity in the association between docosapentaenoic acid and prostate cancer by grade of disease (P = .006); the association was statistically significant for low-grade disease but not high-grade disease. The remaining 11 fatty acids were not statistically associated with total prostate cancer risk., Conclusion: There was no strong evidence that circulating fatty acids are important predictors of prostate cancer risk. It is not clear whether the modest associations of stearic, eicosapentaenoic, and docosapentaenoic acid are causal., (© The Author 2014. Published by Oxford University Press.)

It has been hypothesized that a high intake of dairy protein may increase prostate cancer risk by increasing the production of insulin-like growth factor 1 (IGF-1). Several single nucleotide polymorphisms (SNPs) have been weakly associated with circulating concentrations of IGF-1 and IGF binding protein 3 (IGFBP-3), but none of these SNPs was associated with risk of prostate cancer. We examined whether an association between 16 SNPs associated with circulating IGF-1 or IGFBP-3 concentrations and prostate cancer exists within subgroups defined by dietary protein intake in 5,253 cases and 4,963 controls of European ancestry within the NCI Breast and Prostate Cancer Cohort Consortium (BPC3). The BPC3 includes nested case-control studies within large North-American and European cohorts. Per-allele odds ratios for prostate cancer for the SNPs were compared across tertiles of protein intake, which was expressed as the percentage of energy derived from total, animal, dairy or plant protein sources, using conditional logistic regression models. Total, animal, dairy and plant protein intakes were significantly positively associated with blood IGF-1 (p < 0.01), but not with IGFBP-3 concentrations (p > 0.10) or with risk of prostate cancer (p > 0.20). After adjusting for multiple testing, the SNP-prostate cancer associations did not differ by intakes of protein, although two interactions by intake of plant protein were of marginal statistical significance [SSTR5 (somatostatin receptor 5)-rs197056 (uncorrected p for interaction, 0.001); SSTR5-rs197057 (uncorrected p for interaction, 0.002)]. We found no strong evidence that the associations between 16 IGF pathway SNPs and prostate cancer differed by intakes of dietary protein., (Copyright © 2013 UICC.)

High dairy protein intake has been found to be associated with increased prostate cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC). To further examine this possible relationship, we investigated the hypothesis that a genetic polymorphism in the lactase (LCT) gene might be associated with elevated dairy product intake and increased prostate cancer risk in a case-control study nested in EPIC. The C/T-13910 lactase variant (rs4988235) was genotyped in 630 men with prostate cancer and 873 matched control participants. Dairy product consumption was assessed by diet questionnaire. Odds ratios (ORs) for prostate cancer in relation to lactase genotype were estimated by conditional logistic regression. Lactase genotype frequency varied significantly between countries, with frequencies of the T (lactase persistence) allele ranging from 7% in Greece to 79% in Denmark. Intake of milk and total dairy products varied significantly by lactase genotype after adjustment for recruitment center; adjusted mean intakes of milk were 44.4, 69.8 and 82.3 g/day among men with CC, CT and TT genotypes, respectively. The lactase variant was not significantly associated with prostate cancer risk, both in our data (adjusted OR for TT vs. CC homozygotes: 1.10, 95% CI: 0.76-1.59) and in a meta-analysis of all the published data (combined OR for T allele carriers vs. CC homozygotes: 1.12, 0.96-1.32). These findings show that while variation in the lactase gene is associated with milk intake in men, the lactase polymorphism does not have a large effect on prostate cancer risk., (Copyright © 2012 UICC.)

Background: High circulating insulin-like growth factor-I (IGF-I) concentrations have been associated with increased risk for prostate cancer in several prospective epidemiological studies. In this study, we investigate the association between circulating IGF-I concentration and risk of prostate cancer over the long term in the European Prospective Investigation into Cancer and Nutrition (EPIC) study., Methods: In a nested case-control design, 1,542 incident prostate cancer cases from eight European countries were individually matched to 1,542 controls by study center, age at recruitment, duration of follow-up, time of day, and duration of fasting at blood collection. Conditional logistic regression models were used to calculate risk for prostate cancer associated with IGF-I concentration, overall and by various subgroups., Results: Circulating IGF-I concentration was associated with a significant increased risk for prostate cancer [OR for highest vs. lowest quartile, 1.69; 95% confidence interval (CI), 1.35-2.13; P(trend) = 0.0002]. This positive association did not differ according to duration of follow-up [ORs for highest vs. lowest quartile were 2.01 (1.35-2.99), 1.37 (0.94-2.00), and 1.80 (1.17-2.77) for cancers diagnosed <4, 4-7, and >7 years after blood collection, respectively (P(heterogeneity) = 0.77)] or by stage, grade, and age at diagnosis or age at blood collection (all subgroups P(heterogeneity) >0.05)., Conclusion: In this European population, high circulating IGF-I concentration is positively associated with risk for prostate cancer over the short and long term., Impact: As IGF-I is the only potentially modifiable risk factor so far identified, research into the effects of reducing circulating IGF-I levels on subsequent prostate cancer risk is warranted., (©2012 AACR)

Purpose: Data from prospective epidemiological studies in Asian populations and from experimental studies in animals and cell lines suggest a possible protective association between dietary isoflavones and the development of prostate cancer. We examined the association between circulating concentrations of genistein and prostate cancer risk in a case-control study nested in the European Prospective Investigation into Cancer and Nutrition., Methods: Concentrations of the isoflavone genistein were measured in prediagnostic plasma samples for 1,605 prostate cancer cases and 1,697 matched control participants. Relative risks (RRs) for prostate cancer in relation to plasma concentrations of genistein were estimated by conditional logistic regression., Results: Plasma genistein concentrations were not associated with prostate cancer risk; the multivariate relative risk for men in the highest fifth of genistein compared with men in the lowest fifth was 1.00 (95 % confidence interval: 0.79, 1.27; p linear trend = 0.82). There was no evidence of heterogeneity in this association by age at blood collection, country of recruitment, or cancer stage or histological grade., Conclusion: Plasma genistein concentration was not associated with prostate cancer risk in this large cohort of European men.

Genome-wide association studies (GWAS) have identified many single nucleotide polymorphisms (SNPs) associated with prostate cancer risk. There is limited information on the mechanistic basis of these associations, particularly about whether they interact with circulating concentrations of growth factors and sex hormones, which may be important in prostate cancer etiology. Using conditional logistic regression, the authors compared per-allele odds ratios for prostate cancer for 39 GWAS-identified SNPs across thirds (tertile groups) of circulating concentrations of insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding protein 3 (IGFBP-3), testosterone, androstenedione, androstanediol glucuronide, estradiol, and sex hormone-binding globulin (SHBG) for 3,043 cases and 3,478 controls in the Breast and Prostate Cancer Cohort Consortium. After allowing for multiple testing, none of the SNPs examined were significantly associated with growth factor or hormone concentrations, and the SNP-prostate cancer associations did not differ by these concentrations, although 4 interactions were marginally significant (MSMB-rs10993994 with androstenedione (uncorrected P = 0.008); CTBP2-rs4962416 with IGFBP-3 (uncorrected P = 0.003); 11q13.2-rs12418451 with IGF-1 (uncorrected P = 0.006); and 11q13.2-rs10896449 with SHBG (uncorrected P = 0.005)). The authors found no strong evidence that associations between GWAS-identified SNPs and prostate cancer are modified by circulating concentrations of IGF-1, sex hormones, or their major binding proteins.

Background: Phytanic acid, a fatty acid predominantly obtained from foods high in ruminant fat, may have a biological role in the up-regulation of the protein alpha-methylacyl-coenzyme A racemase, which is overexpressed in prostate cancer tissue., Objective: This study aimed to examine the association between plasma concentrations of phytanic acid and subsequent risk of prostate cancer., Design: Within the European Prospective Investigation into Cancer and Nutrition cohort, 566 incident prostate cancer cases from Germany, Greece, Italy, the Netherlands, Spain, and the United Kingdom were individually matched to 566 controls by study center, age at recruitment, and time of day and duration of fasting at blood collection. Phytanic acid concentrations were measured by using a gas chromatography-mass spectrometry assay., Results: In controls, plasma phytanic acid concentration was strongly correlated with dairy fat intake (r = 0.49, P < 0.0001), varied significantly by country (P for heterogeneity < 0.0001), and decreased with age (P for trend = 0.02) and duration of fasting at blood collection (P for trend = 0.002). There was no significant association of phytanic acid with prostate cancer risk overall (odds ratio for a doubling in concentration: 1.05; 95% CI: 0.91, 1.21; P for trend = 0.53) or by stage or grade of disease. However, in men who had fasted (>3 h) at blood collection, the odds ratio for prostate cancer was 1.27 (95% CI: 1.01, 1.60; P for trend = 0.04)., Conclusion: Plasma phytanic acid concentration is significantly associated with intake of dairy fat but not with overall risk of prostate cancer in this European population.

Results from the majority of studies show little association between circulating concentrations of vitamin D and prostate cancer risk, a finding that has not been demonstrated in a wider European population, however. The authors examined whether vitamin D concentrations were associated with prostate cancer risk in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (1994-2000). Serum concentrations of 25-hydroxyvitamin D were measured in 652 prostate cancer cases matched to 752 controls from 7 European countries after a median follow-up time of 4.1 years. Conditional logistic regression models were used to calculate odds ratios for prostate cancer risk in relation to serum 25-hydroxyvitamin D after standardizing for month of blood collection and adjusting for covariates. No significant association was found between 25-hydroxyvitamin D and risk of prostate cancer (highest vs. lowest quintile: odds ratio = 1.28, 95% confidence interval: 0.88, 1.88; P for trend = 0.188). Subgroup analyses showed no significant heterogeneity by cancer stage or grade, age at diagnosis, body mass index, time from blood collection to diagnosis, or calcium intake. In summary, the results of this large nested case-control study provide no evidence in support of a protective effect of circulating concentrations of vitamin D on the risk of prostate cancer.

Few studies have examined the association between dietary fiber intake and prostate cancer risk. We evaluated the association between dietary fiber intake and the risk of prostate cancer among 142,590 men in the European Prospective Investigation into Cancer and Nutrition (EPIC). Consumption of dietary fiber (total, cereal, fruit and vegetable fiber) was estimated by validated dietary questionnaires and calibrated using 24-hr dietary recalls. Incidence rate ratios were estimated using Cox regression and adjusted for potential confounding factors. During an average of 8.7 years follow-up, prostate cancer was diagnosed in 2,747 men. Overall, there was no association between dietary fiber intake (total, cereal, fruit or vegetable fiber) and prostate cancer risk, although calibrated intakes of total fiber and fruit fiber were associated with nonstatistically significant reductions in risk. There was no association between fiber derived from cereals or vegetables and risk and no evidence for heterogeneity in any of the risk estimates by stage or grade of disease. Our results suggest that dietary fiber intake is not associated with prostate cancer risk.

Background: Some evidence indicates that a low selenium intake may be associated with an increased risk of prostate cancer., Objective: The aim of this study was to investigate the association of plasma selenium concentration with subsequent prostate cancer risk and to examine this association by stage and grade of disease and other factors., Design: A nested case-control study was performed among men in the European Prospective Investigation into Cancer and Nutrition (EPIC). The association between plasma selenium concentration and prostate cancer risk was assessed in 959 men with incident prostate cancer and 1059 matched controls., Results: Overall, plasma selenium concentration was not associated with prostate cancer risk; the multivariate relative risk for men in the highest fifth of selenium concentration compared with the lowest fifth was 0.96 (95% CI: 0.70, 1.31; P for trend = 0.25). There were no significant differences in the association of plasma selenium with risk when analyzed by stage or grade of disease. Similarly, the association of selenium with risk did not differ by smoking status or by plasma alpha- or gamma-tocopherol concentration., Conclusion: Plasma selenium concentration was not associated with prostate cancer risk in this large cohort of European men.

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, alpha-linolenic, and eicosapentaenoic acids and risk of high-grade prostate cancer., Conclusion: The associations between palmitic, stearic, myristic, alpha-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.

Background: Some, but not all, published results have shown an association between circulating blood levels of some insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) and the subsequent risk for prostate cancer., Purpose: To assess the association between levels of IGFs and IGFBPs and the subsequent risk for prostate cancer., Data Sources: Studies identified in PubMed, Web of Science, and CancerLit., Study Selection: The principal investigators of all studies that published data on circulating concentrations of sex steroids, IGFs, or IGFBPs and prostate cancer risk using prospectively collected blood samples were invited to collaborate., Data Extraction: Investigators provided individual participant data on circulating concentrations of IGF-I, IGF-II, IGFBP-II, and IGFBP-III and participant characteristics to a central data set in Oxford, United Kingdom., Data Synthesis: The study included data on 3700 men with prostate cancer and 5200 control participants. On average, case patients were 61.5 years of age at blood collection and received a diagnosis of prostate cancer 5 years after blood collection. The greater the serum IGF-I concentration, the greater the subsequent risk for prostate cancer (odds ratio [OR] in the highest vs. lowest quintile, 1.38 [95% CI, 1.19 to 1.60]; P < 0.001 for trend). Neither IGF-II nor IGFBP-II concentrations were associated with prostate cancer risk, but statistical power was limited. Insulin-like growth factor I and IGFBP-III were correlated (r = 0.58), and although IGFBP-III concentration seemed to be associated with prostate cancer risk, this was secondary to its association with IGF-I levels. Insulin-like growth factor I concentrations seemed to be more positively associated with low-grade than high-grade disease; otherwise, the association between IGFs and IGFBPs and prostate cancer risk had no statistically significant heterogeneity related to stage or grade of disease, time between blood collection and diagnosis, age and year of diagnosis, prostate-specific antigen level at recruitment, body mass index, smoking, or alcohol intake., Limitations: Insulin-like growth factor concentrations were measured in only 1 sample for each participant, and the laboratory methods to measure IGFs differed in each study. Not all patients had disease stage or grade information, and the diagnosis of prostate cancer may differ among the studies., Conclusion: High circulating IGF-I concentrations are associated with a moderately increased risk for prostate cancer.

Background: Findings from early observational studies have suggested that the intake of dietary fat might be a contributing factor in the etiology of prostate cancer. However, the results from more recent prospective studies do not support this hypothesis, and the possible association between different food sources of fat and prostate cancer risk also remains unclear., Objective: The objectives were to assess whether intakes of dietary fat, subtypes of fat, and fat from animal products were associated with prostate cancer risk., Design: This was a multicenter prospective study of 142,520 men in the European Prospective Investigation into Cancer and Nutrition (EPIC). Dietary fat intake was estimated with the use of country-specific validated food questionnaires. The association between dietary fat and risk of prostate cancer was assessed by using Cox regression, stratified by recruitment center and adjusted for height, weight, smoking, education, marital status, and energy intake., Results: After a median follow-up time of 8.7 y, prostate cancer was diagnosed in 2727 men. There was no significant association between dietary fat (total, saturated, monounsaturated, and polyunsaturated fat and the ratio of polyunsaturated to saturated fat) and risk of prostate cancer. The hazard ratio for prostate cancer for the highest versus the lowest quintile of total fat intake was 0.96 (95% CI: 0.84, 1.09; P for trend = 0.155). There were no significant associations between prostate cancer risk and fat from red meat, dairy products, and fish., Conclusion: The results from this large multicenter study suggest that there is no association between dietary fat and prostate cancer risk.

Background: Sex hormones in serum have been hypothesized to influence the risk of prostate cancer. We performed a collaborative analysis of the existing worldwide epidemiologic data to examine these associations in a uniform manner and to provide more precise estimates of risks., Methods: Data on serum concentrations of sex hormones from 18 prospective studies that included 3886 men with incident prostate cancer and 6438 control subjects were pooled by the Endogenous Hormones and Prostate Cancer Collaborative Group. Relative risks (RRs) of prostate cancer by fifths of serum hormone concentration were estimated by use of conditional logistic regression with stratification by study, age at recruitment, and year of recruitment. All statistical tests were two-sided., Results: No associations were found between the risk of prostate cancer and serum concentrations of testosterone, calculated free testosterone, dihydrotestosterone, dehydroepiandrosterone sulfate, androstenedione, androstanediol glucuronide, estradiol, or calculated free estradiol. The serum concentration of sex hormone-binding globulin was modestly inversely associated with prostate cancer risk (RR in the highest vs lowest fifth = 0.86, 95% confidence interval = 0.75 to 0.98; P(trend) = .01). There was no statistical evidence of heterogeneity among studies, and adjustment for potential confounders made little difference to the risk estimates., Conclusions: In this collaborative analysis of the worldwide data on endogenous hormones and prostate cancer risk, serum concentrations of sex hormones were not associated with the risk of prostate cancer.

Background: Determinants of one-carbon metabolism, such as folate and vitamin B(12), have been implicated in cancer development. Previous studies have not provided conclusive evidence for the importance of circulating concentrations of folate and vitamin B(12) in prostate cancer etiology. The aim of the present study was to investigate the relationship between prostate cancer risk and circulating concentrations of folate and vitamin B(12) in a large prospective cohort., Methods: We analyzed circulating concentrations of folate and vitamin B(12) in 869 cases and 1,174 controls, individually matched on center, age, and date of recruitment, nested within the European Prospective Investigation into Cancer and Nutrition cohort. Relative risks (RR) for prostate cancer were estimated using conditional logistic regression models., Results: Overall, no significant associations were observed for circulating concentrations of folate (P(trend) = 0.62) or vitamin B(12) (P(trend) = 0.21) with prostate cancer risk. RRs for a doubling in folate and vitamin B(12) concentrations were 1.03 [95% confidence interval (95% CI), 0.92-1.16] and 1.12 (95% CI, 0.94-1.35), respectively. In the subgroup of cases diagnosed with advanced stage prostate cancer, elevated concentrations of vitamin B(12) were associated with increased risk (RR for a doubling in concentration, 1.69; 95% CI, 1.05-2.72, P(trend) = 0.03). No other subgroup analyses resulted in a statistically significant association., Conclusion: This study does not provide strong support for an association between prostate cancer risk and circulating concentrations of folate or vitamin B(12). Elevated concentrations of vitamin B(12) may be associated with an increased risk for advanced stage prostate cancer, but this association requires examination in other large prospective studies.

We examined the hypothesis that serum concentrations of circulating androgens and sex hormone binding globulin (SHBG) are associated with risk for prostate cancer in a case-control study nested in the European Prospective Investigation into Cancer and Nutrition (EPIC). Concentrations of androstenedione, testosterone, androstanediol glucuronide and SHBG were measured in serum samples for 643 prostate cancer cases and 643 matched control participants, and concentrations of free testosterone were calculated. Conditional logistic regression models were used to calculate odds ratios for risk of prostate cancer in relation to the serum concentration of each hormone. After adjustment for potential confounders, there was no significant association with overall risk for prostate cancer for serum total or free testosterone concentrations (highest versus the lowest thirds: OR, 1.02; 95% CI, 0.73-1.41 and OR, 1.07, 95% CI, 0.74-1.55, respectively) or for other androgens or SHBG. Subgroup analyses showed significant heterogeneity for androstenedione by cancer stage, with a significant inverse association of androstenedione concentration and risk for advanced prostate cancer. There were also weak positive associations between free testosterone concentration and risk for total prostate cancer among younger men and risk for high-grade disease. In summary, in this large nested case-control study, concentrations of circulating androgens or SHBG were not strongly associated with risk for total prostate cancer. However, our findings are compatible with a positive association of free testosterone with risk in younger men and possible heterogeneity in the association with androstenedione concentration by stage of disease; these findings warrant further investigation., ((c) 2007 Wiley-Liss, Inc.)

Background: Previous studies suggest that high plasma concentrations of carotenoids, retinol, or tocopherols may reduce the risk of prostate cancer., Objective: We aimed to examine the associations between plasma concentrations of 7 carotenoids, retinol, alpha-tocopherol, and gamma-tocopherol and prostate cancer risk., Design: A total of 137,001 men in 8 European countries participated. After a mean of 6 y, 966 incident cases of prostate cancer with plasma were available. A total of 1064 control subjects were selected and were matched for study center, age, and date of recruitment. The relative risk of prostate cancer was estimated by conditional logistic regression, which was adjusted for smoking status, alcohol intake, body mass index, marital status, physical activity, and education level., Results: Overall, none of the micronutrients examined were significantly associated with prostate cancer risk. For lycopene and the sum of carotenoids, there was evidence of heterogeneity between the associations with risks of localized and advanced disease. These carotenoids were not associated with the risk of localized disease but were inversely associated with the risk of advanced disease. The risk of advanced disease for men in the highest fifth of plasma concentrations compared with men in the lowest fifth was 0.40 (95% CI: 0.19, 0.88) for lycopene and 0.35 (95% CI: 0.17, 0.78) for the sum of carotenoids., Conclusions: We observed no associations between plasma concentrations of carotenoids, retinol, or tocopherols and overall prostate cancer risk. The inverse associations of lycopene and the sum of carotenoids with the risk of advanced disease may involve a protective effect, an association of dietary choice with delayed detection of prostate cancer, reverse causality, or other factors.

Background: Some studies suggest that elevated serum insulin-like growth factor (IGF)-I concentrations are associated with an increased risk of prostate cancer and, in particular, with an increased risk of advanced-stage prostate cancer., Methods: We analyzed the association between prediagnostic serum concentrations of IGF-I and IGF-binding protein-3 (IGFBP-3) and prostate cancer risk in a case-control study nested in the European Prospective Investigation into Cancer and Nutrition. This study includes 630 incident prostate cancer cases and 630 matched control subjects. Odds ratios and their 95% confidence intervals (95% CI) were calculated for prostate cancer risk associated with increasing IGF-I and IGFBP-3 concentrations using conditional logistic regression., Results: The risk of total prostate cancer in the highest versus the lowest third of serum peptide concentration was 1.35 (95% CI, 0.99-1.82; Ptrend = 0.08) for IGF-I, 1.39 (95% CI, 1.02-1.89; Ptrend = 0.12) for the IGF-I residuals after adjusting for IGFBP-3, 1.22 (95% CI, 0.92-1.64; Ptrend = 0.38) for IGFBP-3, and 1.01 (95% CI, 0.74-1.37; Ptrend = 0.75) for the IGFBP-3 residuals after adjusting for IGF-I. There was no significant difference in the association of peptide hormones and prostate cancer by stage of disease, although the association of serum IGF-I concentration with risk was slightly stronger for advanced-stage disease; the odds ratio for the highest versus the lowest third was 1.65 (95% CI, 0.88-3.08; Ptrend = 0.21) for IGF-I and 1.76 (95% CI, 0.92-3.40; Ptrend = 0.11) for IGF-I adjusted for IGFBP-3., Conclusions: In this large nested case-control study, serum IGF-I concentration is not strongly associated with prostate cancer risk, although the results are compatible with a small increase in risk, particularly for advanced-stage disease; no association for IGFBP-3 was observed.

Background and Aims: It has been hypothesized that some aspect of a traditional 'Asian' diet, that is low in animal products and high in soya, may be associated with a reduced risk of prostate cancer. This study aimed to examine the association between dietary intake and prostate cancer risk among 18,115 men in Hiroshima and Nagasaki, Japan, using prospective data from the Life Span Study., Methods: Subjects completed a food-frequency questionnaire at baseline (1963, 1965 and/or 1979) and were followed for incident prostate cancer until the end of 1996. During this time, 196 incident prostate cancer cases were identified after 252,602 person-years of observation. Poisson regression was used to calculate incidence rates for each dietary factor after adjustment for age, calendar period, city of residence, radiation dose and education level., Results: Fish intake was significantly associated with an increased risk of prostate cancer; men who consumed fish more than four times per week had a 54 increased risk of developing prostate cancer compared with men who ate fish less than twice per week (RR = 1.54; 95% CI, 1.03-2.31). No other food items, including soya products, were significantly associated with prostate cancer risk., Conclusions: These data suggest that dietary factors may not be strong determinants of prostate cancer in these Japanese men, although the increased risk associated with a high consumption of fish warrants further study.

We examined the association between self-reported consumption of fruits and vegetables and prostate cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC). Data on food consumption and complete follow-up for cancer incidence were available for 130544 men in 7 countries recruited into EPIC between 1993 and 1999. After an average of 4.8 years of follow-up, there were 1104 incident cases of prostate cancer. The associations of consumption of total fruits, total vegetables, cruciferous vegetables and combined total fruits and vegetables with prostate cancer risk were examined using Cox regression, stratified for recruitment center and adjusted for height, weight and energy intake. There was a wide range in consumption of fruits and vegetables: mean intakes (g/day) in the bottom and top fifths of the distribution, as estimated from 24-hr recalls in a subsample of participants, were 53.2 and 410.7 for fruits, 97.1 and 242.1 for vegetables and 169.0 and 633.7 for fruits and vegetables combined. No significant associations between fruit and vegetable consumption and prostate cancer risk were observed. Relative risks (95% confidence intervals) in the top fifth of the distribution of consumption, compared to the bottom fifth, were 1.06 (0.84-1.34) for total fruits, 1.00 (0.81-1.22) for total vegetables and 1.00 (0.79-1.26) for total fruits and vegetables combined; intake of cruciferous vegetables was not associated with risk. These results suggest that total consumption of fruits and vegetables is not associated with the risk for prostate cancer., (Copyright 2003 Wiley-Liss, Inc.)