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Background: Smoking is not associated with prostate cancer incidence in most studies, but associations between smoking and fatal prostate cancer have been reported., Methods: During 1992 and 2000, lifestyle information was assessed via questionnaires and personal interview in a cohort of 145,112 European men. Until 2009, 4623 incident cases of prostate cancer were identified, including 1517 cases of low-grade, 396 cases of high grade, 1516 cases of localised, 808 cases of advanced disease, and 432 fatal cases. Multivariable Cox proportional hazards regression models were used to examine the association of smoking status, smoking intensity, and smoking duration with the risk of incident and fatal prostate cancer., Results: Compared with never smokers, current smokers had a reduced risk of prostate cancer (RR=0.90, 95% CI: 0.83-0.97), which was statistically significant for localised and low-grade disease, but not for advanced or high-grade disease. In contrast, heavy smokers (25+ cigarettes per day) and men who had smoked for a long time (40+ years) had a higher risk of prostate cancer death (RR=1.81, 95% CI: 1.11-2.93; RR=1.38, 95% CI: 1.01-1.87, respectively)., Conclusion: The observation of an increased prostate cancer mortality among heavy smokers confirms the results of previous prospective studies.

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.

Objective: High intake of whole-grain products may protect against prostate cancer, but overall evidence is limited and inconclusive. The aim of the present study was to investigate the relationship between the intake of whole-grain products and risk of prostate cancer in a large prospective cohort., Methods: A total of 26,691 men aged 50-64 years participated in the Diet, Cancer and Health cohort study and provided information about diet and potential prostate cancer risk factors. During a median follow-up of 12.4 years, we identified 1,081 prostate cancer cases. Associations between whole-grain product intake and prostate cancer incidence were analyzed using Cox's regression model., Results: Overall, there was no association between total intake of whole-grain products and prostate cancer risk (adjusted incidence rate ratio per 50 g day(-1): 1.00 (95% confidence interval: 0.96, 1.05)) as well as between intake of the specific whole-grain products: whole-grain rye bread, whole-grain bread, and oatmeal, and risk of prostate cancer. No risk estimates did differ according to either stage or grade of disease., Conclusions: Results from this prospective study suggest that higher intakes of total or specific whole-grain products are not associated with risk of prostate cancer in a population of Danish middle-aged men.

The evidence concerning the possible association between physical activity and the risk of prostate cancer is inconsistent and additional data are needed. We examined the association between risk of prostate cancer and physical activity at work and in leisure time in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. In our study, including 127,923 men aged 20-97 years from 8 European countries, 2,458 cases of prostate cancer were identified during 8.5 years of followup. Using the Cox proportional hazards model, we investigated the associations between prostate cancer incidence rate and occupational activity and leisure time activity in terms of participation in sports, cycling, walking and gardening; a metabolic equivalent (MET) score based on weekly time spent on the 4 activities; and a physical activity index. MET hours per week of leisure time activity, higher score in the physical activity index, participation in any of the 4 leisure time activities, and the number of leisure time activities in which the participants were active were not associated with prostate cancer incidence. However, higher level of occupational physical activity was associated with lower risk of advanced stage prostate cancer (p(trend) = 0.024). In conclusion, our data support the hypothesis of an inverse association between advanced prostate cancer risk and occupational physical activity, but we found no support for an association between prostate cancer risk and leisure time physical activity.

We examined plasma concentrations of phyto-oestrogens in relation to risk for subsequent prostate cancer in a case-control study nested in the European Prospective Investigation into Cancer and Nutrition. Concentrations of isoflavones genistein, daidzein and equol, and that of lignans enterolactone and enterodiol, were measured in plasma samples for 950 prostate cancer cases and 1042 matched control participants. Relative risks (RRs) for prostate cancer in relation to plasma concentrations of these phyto-oestrogens were estimated by conditional logistic regression. Higher plasma concentrations of genistein were associated with lower risk of prostate cancer: RR among men in the highest vs the lowest fifth, 0.71 (95% confidence interval (CI) 0.53-0.96, P trend=0.03). After adjustment for potential confounders this RR was 0.74 (95% CI 0.54-1.00, P trend=0.05). No statistically significant associations were observed for circulating concentrations of daidzein, equol, enterolactone or enterodiol in relation to overall risk for prostate cancer. There was no evidence of heterogeneity in these results by age at blood collection or country of recruitment, nor by cancer stage or grade. These results suggest that higher concentrations of circulating genistein may reduce the risk of prostate cancer but do not support an association with plasma lignans.

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: Body size has been hypothesized to influence the risk of prostate cancer; however, most epidemiologic studies have relied on body mass index (BMI) to assess adiposity, whereas only a few studies have examined whether body fat distribution predicts prostate cancer., Methods: We examined the association of height, BMI, waist and hip circumference, and waist-hip ratio with prostate cancer risk among 129,502 men without cancer at baseline from 8 countries of the European Prospective Investigation into Cancer and Nutrition (EPIC), using Cox regression, with age as time metric, stratifying by study center and age at recruitment, and adjusting for education, smoking status, alcohol consumption, and physical activity., Results: During a mean follow-up of 8.5 years, 2,446 men developed prostate cancer. Waist circumference and waist-hip ratio were positively associated with risk of advanced disease. The relative risk of advanced prostate cancer was 1.06 (95% confidence interval, 1.01-1.1) per 5-cm-higher waist circumference and 1.21 (95% confidence interval, 1.04-1.39) per 0.1-unit-higher waist-hip ratio. When stratified by BMI, waist circumference and waist-hip ratio were positively related to risk of total, advanced, and high-grade prostate cancer among men with lower but not among those with higher BMI (Pinteraction for waist with BMI, 0.25, 0.02, and 0.05, respectively; Pinteraction for waist-hip ratio with BMI, 0.27, 0.22, and 0.14; respectively)., Conclusions: These data suggest that abdominal adiposity may be associated with an increased risk of advanced prostate cancer. This association may be stronger among individuals with lower BMI; however, this finding needs confirmation in future studies.

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.

We investigated the effects of socioeconomic, demographic and health-related indicators on the incidence of and survival from prostate and testicular cancer diagnosed 1994-2003 with follow-up through 2006 in Denmark using information from nationwide registers. The analyses were based on data on 8279 men with prostate cancer and 1770 with testicular cancer in a cohort of 3.22 million persons born between 1925 and 1973 and aged >or=30 years. We found that men with higher education and the highest disposable income had the highest incidence of prostate cancer. The 1-year and 5-year relative survival after prostate cancer were best amongst men of the highest socioeconomic position. We found no substantial social gradients in the incidence of or survival from testicular cancer.

We examined consumption of animal foods, protein and calcium in relation to risk of prostate cancer among 142 251 men in the European Prospective Investigation into Cancer and Nutrition. Associations were examined using Cox regression, stratified by recruitment centre and adjusted for height, weight, education, marital status and energy intake. After an average of 8.7 years of follow-up, there were 2727 incident cases of prostate cancer, of which 1131 were known to be localised and 541 advanced-stage disease. A high intake of dairy protein was associated with an increased risk, with a hazard ratio for the top versus the bottom fifth of intake of 1.22 (95% confidence interval (CI): 1.07-1.41, P(trend)=0.02). After calibration to allow for measurement error, we estimated that a 35-g day(-1) increase in consumption of dairy protein was associated with an increase in the risk of prostate cancer of 32% (95% CI: 1-72%, P(trend)=0.04). Calcium from dairy products was also positively associated with risk, but not calcium from other foods. The results support the hypothesis that a high intake of protein or calcium from dairy products may increase the 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.

Alcohol is a risk factor for several types of cancer. However, the results for prostate cancer have been inconsistent, with most studies showing no association. Within the European Prospective Investigation into Cancer and Nutrition, detailed information were collected from 142,607 male participants on the intake of alcoholic beverages at recruitment (for 100% of the cohort) and over lifetime (for 76% of the cohort) between 1992 and 2000. During a median follow-up of 8.7 years, 2,655 prostate cancer cases were observed. Multivariate Cox proportional hazard models were used to examine the association of alcohol consumption at recruitment and average lifetime alcohol consumption with prostate cancer adjusted for age, center, smoking, height, weight, physical activity, and nonalcohol energy intake. Overall, neither alcohol consumption at baseline nor average lifetime alcohol consumption was associated with the risk for prostate cancer in this cohort of men. Men who consumed >or=60 g alcohol per day had a relative risk of 0.88 [95% confidence interval (95% CI) 0.72-1.08] compared with men with an intake of 0.1-4.9 g/d; the respective relative risk for average lifetime intake was 1.09 (95% CI, 0.86-1.39). For advanced prostate cancer (n = 537), the relative risks for >or=60 and 0.1-4.9 g alcohol per day at baseline were 0.98 (95% CI, 0.66-1.44) and 1.28 (95% CI, 0.79-2-07), respectively, for average lifetime intake. No statistically significant association was observed for alcohol intake from specific alcoholic beverages. Our results indicate no association between the consumption of alcohol and prostate cancer in this cohort of European men.

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.