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BackgroundA previous analysis of the placebo arm of the Prostate Cancer Prevention Trial (PCPT) reported 82% overall prevalence of intraprostatic inflammation and identified a link between inflammation and higher-grade prostate cancer and serum PSA. Here, we studied these associations in the PCPT finasteride arm.MethodsProstate cancer cases (N = 197) detected either on a clinically indicated biopsy or on protocol-directed end-of-study biopsy, and frequency-matched controls (N = 248) with no cancer on an end-of-study biopsy were sampled from the finasteride arm. Inflammation in benign prostate tissue was visually assessed using digital images of hematoxylin and eosin-stained sections. Logistic regression was used for statistical analysis.ResultsIn the finasteride arm, 91.6% of prostate cancer cases and 92.4% of controls had at least one biopsy core with inflammation in benign areas (P < 0.001 for difference compared with placebo arm). Overall, the odds of prostate cancer did not differ by prevalence [OR, 0.90; 95% confidence interval (CI), 0.44-1.84] or extent (P trend = 0.68) of inflammation. Inflammation was not associated with higher-grade disease (prevalence: OR, 1.07; 95% CI, 0.43-2.69). Furthermore, mean PSA concentration did not differ by the prevalence or extent of inflammation in either cases or controls.ConclusionThe prevalence of intraprostatic inflammation was higher in the finasteride than placebo arm of the PCPT, with no association with higher-grade prostate cancer.ImpactFinasteride may attenuate the association between inflammation and higher-grade prostate cancer. Moreover, the missing link between intraprostatic inflammation and PSA suggests that finasteride may reduce inflammation-associated PSA elevation.

BackgroundThe intake of nutrients with antioxidant properties is hypothesized to augment antioxidant defenses, decrease oxidant damage to tissues, and attenuate age-related rate of decline in lung function. The objective was to determine whether long-term intervention with selenium and/or vitamin E supplements attenuates the annual rate of decline in lung function, particularly in cigarette smokers.MethodsThe Respiratory Ancillary Study (RAS) tested the single and joint effects of selenium (200 μg/d L-selenomethionine) and vitamin E (400 IU/day all rac-α-tocopheryl acetate) in a randomized double-blind placebo-controlled trial. At the end of the intervention, 1,641 men had repeated pulmonary function tests separated by an average of 3 years. Linear mixed-effects regression models estimated the effect of intervention on annual rate of decline in lung function.ResultsCompared to placebo, intervention had no main effect on either forced expiratory volume in the first second (FEV1) or forced expiratory flow (FEF25-75). There was no evidence for a smoking by treatment interaction for FEV1, but selenium attenuated rate of decline in FEF25-75 in current smokers (P = 0.0219). For current smokers randomized to selenium, annual rate of decline in FEF25-75 was similar to the annual decline experienced by never smokers randomized to placebo, with consistent effects for selenium alone and combined with vitamin E.ConclusionsAmong all men, there was no effect of selenium and/or vitamin E supplementation on rate of lung function decline. However, current smokers randomized to selenium had an attenuated rate of decline in FEF25-75, a marker of airflow.Trial registrationClinicaltrials.gov identifier: NCT00241865 .

Inflammation may play an etiologic role in prostate cancer. Several dietary factors influence inflammation; studies have shown that long-chain n-3 polyunsaturated fatty acids are anti-inflammatory, whereas n-6 and trans fatty acids are proinflammatory. We evaluated whether serum phospholipid n-3, n-6, and trans fatty acids were associated with intraprostatic inflammation, separately in 191 prostate cancer cases and 247 controls from the placebo arm of the Prostate Cancer Prevention Trial (PCPT). Men without a prostate cancer diagnosis underwent prostate biopsy at trial end, and benign prostate tissue inflammation was evaluated in approximately three biopsy cores per man; this was expressed as no, some, or all cores with inflammation. In controls, serum eicosapentaenoic acid [OR of all cores with inflammation versus none (95% CI), 0.35 (0.14-0.89)] and docosahexaenoic acid [OR (95% CI), 0.42 (0.17-1.02)] were inversely associated with, whereas linoleic acid [OR (95% CI), 3.85 (1.41-10.55)] was positively associated with intraprostatic inflammation. Serum trans fatty acids were not associated with intraprostatic inflammation. No significant associations were observed in cases; however, we could not rule out a positive association with linoleic acid and an inverse association with arachidonic acid. Thus, in the PCPT, we found that serum n-3 fatty acids were inversely, n-6 fatty acids were positively, and trans fatty acids were not associated with intraprostatic inflammation in controls. Although, in theory, inflammation could mediate associations of serum fatty acids with prostate cancer risk, our findings cannot explain the epidemiologic associations observed with n-3 and n-6 fatty acids.

ObjectiveTo evaluate the effect of finasteride on serum androst-4-ene-3,17-dione (androstenedione) and its association with prostate cancer risk among subjects who participated in the Prostate Cancer Prevention Trial.MethodsWe analyzed serum androstenedione levels in 317 prostate cancer cases and 353 controls, nested in the Prostate Cancer Prevention Trial, a randomized placebo-controlled trial that found finasteride decreased prostate cancer risk. Androstenedione is the second most important circulating androgen in men besides testosterone and also a substrate for 5α-reductase enzyme.ResultsWe observed a 22% increase in androstenedione levels compared with the baseline values in subjects who were treated with finasteride for 3 years. This significant increase did not vary by case-control status. Adjusted odds ratio and 95% confidence interval for the third tertile of absolute change in androstenedione levels compared with the first tertile were 0.42 (95% confidence interval, 0.19-0.94) for low-grade (Gleason score

The nitrogen isotope ratio (δ(15)N) of RBCs has been proposed as a biomarker of marine food intake in Yup'ik people based on strong associations with RBC eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). However, EPA and DHA derive from marine fats, whereas elevated δ(15)N derives from marine protein, and these dietary components may have different biologic effects. Whether δ(15)N is similarly associated with chronic disease risk factors compared with RBC EPA and DHA is not known. We used covariate-adjusted linear models to describe biomarker associations with chronic disease risk factors in Yup'ik people, first in a smaller (n = 363) cross-sectional study population using RBC EPA, DHA, and δ(15)N, and then in a larger (n = 772) cross-sectional study population using δ(15)N only. In the smaller sample, associations of RBC EPA, DHA, and δ(15)N with obesity and chronic disease risk factors were similar in direction and significance: δ(15)N was positively associated with total, HDL, and LDL cholesterol, apolipoprotein A-I, and insulin-like growth factor binding protein-3 (IGFBP-3), and inversely associated with triglycerides. Based on comparisons between covariate-adjusted β-coefficients, EPA was more strongly associated with circulating lipids and lipoproteins, whereas δ(15)N was more strongly associated with adipokines, the inflammatory marker interleukin-6, and IGFBP-3. In the larger sample there were new findings for this population: δ(15)N was inversely associated with blood pressure and there was a significant association (with inverse linear and positive quadratic terms) with adiponectin. In conclusion, δ(15)N is a valid measure for evaluating associations between EPA and DHA intake and chronic disease risk in Yup'ik people and may be used in larger studies. By measuring δ(15)N, we report beneficial associations of marine food intake with blood pressure and adiponectin, which may contribute to a lower incidence of some chronic diseases in Yup'ik people.

BackgroundChronic inflammation is hypothesized to influence prostate cancer development, although a definitive link has not been established.MethodsProstate cancer cases (N = 191) detected on a for-cause (clinically indicated) or end-of-study (protocol directed) biopsy, and frequency-matched controls (N = 209), defined as negative for cancer on an end-of-study biopsy, were sampled from the placebo arm of the Prostate Cancer Prevention Trial. Inflammation prevalence and extent in benign areas of biopsy cores were visually assessed using digital images of hematoxylin and eosin-stained sections. Logistic regression was used to estimate associations.ResultsOf note, 86.2% of cases and 78.2% of controls had at least one biopsy core (of three assessed) with inflammation in benign areas, most of which was chronic. Men who had at least one biopsy core with inflammation had 1.78 [95% confidence interval (CI), 1.04-3.06] times the odds of prostate cancer compared with men who had zero cores with inflammation. The association was stronger for high-grade disease (Gleason sum 7-10, N = 94; OR, 2.24; 95% CI, 1.06-4.71). These patterns were present when restricting to cases and controls in whom intraprostatic inflammation was the least likely to have influenced biopsy recommendation because their prostate-specific antigen (PSA) was low (

The nitrogen isotope ratio (δ(15)N) of RBCs has been proposed as a biomarker of marine food intake in Yup'ik people based on strong associations with RBC eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). However, EPA and DHA derive from marine fats, whereas elevated δ(15)N derives from marine protein, and these dietary components may have different biologic effects. Whether δ(15)N is similarly associated with chronic disease risk factors compared with RBC EPA and DHA is not known. We used covariate-adjusted linear models to describe biomarker associations with chronic disease risk factors in Yup'ik people, first in a smaller (n = 363) cross-sectional study population using RBC EPA, DHA, and δ(15)N, and then in a larger (n = 772) cross-sectional study population using δ(15)N only. In the smaller sample, associations of RBC EPA, DHA, and δ(15)N with obesity and chronic disease risk factors were similar in direction and significance: δ(15)N was positively associated with total, HDL, and LDL cholesterol, apolipoprotein A-I, and insulin-like growth factor binding protein-3 (IGFBP-3), and inversely associated with triglycerides. Based on comparisons between covariate-adjusted β-coefficients, EPA was more strongly associated with circulating lipids and lipoproteins, whereas δ(15)N was more strongly associated with adipokines, the inflammatory marker interleukin-6, and IGFBP-3. In the larger sample there were new findings for this population: δ(15)N was inversely associated with blood pressure and there was a significant association (with inverse linear and positive quadratic terms) with adiponectin. In conclusion, δ(15)N is a valid measure for evaluating associations between EPA and DHA intake and chronic disease risk in Yup'ik people and may be used in larger studies. By measuring δ(15)N, we report beneficial associations of marine food intake with blood pressure and adiponectin, which may contribute to a lower incidence of some chronic diseases in Yup'ik people.

BackgroundThe Selenium and Vitamin E Cancer Prevention Trial found no effect of selenium supplementation on prostate cancer (PCa) risk but a 17% increased risk from vitamin E supplementation. This case-cohort study investigates effects of selenium and vitamin E supplementation conditional upon baseline selenium status.MethodsThere were 1739 total and 489 high-grade (Gleason 7-10) PCa cases and 3117 men in the randomly selected cohort. Proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for effects of supplementation within quintiles of baseline toenail selenium. Cox proportional hazards models were used to estimate hazard ratios, and all statistical tests are two-sided.ResultsToenail selenium, in the absence of supplementation, was not associated with PCa risk. Selenium supplementation (combined selenium only and selenium + vitamin E arms) had no effect among men with low selenium status (

BackgroundStudies of dietary ω-3 fatty acid intake and prostate cancer risk are inconsistent; however, recent large prospective studies have found increased risk of prostate cancer among men with high blood concentrations of long-chain ω-3 polyunsaturated fatty acids ([LCω-3PUFA] 20:5ω3; 22:5ω3; 22:6ω3]. This case-cohort study examines associations between plasma phospholipid fatty acids and prostate cancer risk among participants in the Selenium and Vitamin E Cancer Prevention Trial.MethodsCase subjects were 834 men diagnosed with prostate cancer, of which 156 had high-grade cancer. The subcohort consisted of 1393 men selected randomly at baseline and from within strata frequency matched to case subjects on age and race. Proportional hazards models estimated hazard ratios (HR) and 95% confidence intervals (CI) for associations between fatty acids and prostate cancer risk overall and by grade. All statistical tests were two-sided.ResultsCompared with men in the lowest quartiles of LCω-3PUFA, men in the highest quartile had increased risks for low-grade (HR = 1.44, 95% CI = 1.08 to 1.93), high-grade (HR = 1.71, 95% CI = 1.00 to 2.94), and total prostate cancer (HR = 1.43, 95% CI = 1.09 to 1.88). Associations were similar for individual long-chain ω-3 fatty acids. Higher linoleic acid (ω-6) was associated with reduced risks of low-grade (HR = 0.75, 95% CI = 0.56 to 0.99) and total prostate cancer (HR = 0.77, 95% CI = 0.59 to 1.01); however, there was no dose response.ConclusionsThis study confirms previous reports of increased prostate cancer risk among men with high blood concentrations of LCω-3PUFA. The consistency of these findings suggests that these fatty acids are involved in prostate tumorigenesis. Recommendations to increase LCω-3PUFA intake should consider its potential risks.

ContextSecondary analyses of 2 randomized controlled trials and supportive epidemiologic and preclinical data indicated the potential of selenium and vitamin E for preventing prostate cancer.ObjectiveTo determine whether selenium, vitamin E, or both could prevent prostate cancer and other diseases with little or no toxicity in relatively healthy men.Design, setting, and participantsA randomized, placebo-controlled trial (Selenium and Vitamin E Cancer Prevention Trial [SELECT]) of 35,533 men from 427 participating sites in the United States, Canada, and Puerto Rico randomly assigned to 4 groups (selenium, vitamin E, selenium + vitamin E, and placebo) in a double-blind fashion between August 22, 2001, and June 24, 2004. Baseline eligibility included age 50 years or older (African American men) or 55 years or older (all other men), a serum prostate-specific antigen level of 4 ng/mL or less, and a digital rectal examination not suspicious for prostate cancer.InterventionsOral selenium (200 microg/d from L-selenomethionine) and matched vitamin E placebo, vitamin E (400 IU/d of all rac-alpha-tocopheryl acetate) and matched selenium placebo, selenium + vitamin E, or placebo + placebo for a planned follow-up of minimum of 7 years and a maximum of 12 years.Main outcome measuresProstate cancer and prespecified secondary outcomes, including lung, colorectal, and overall primary cancer.ResultsAs of October 23, 2008, median overall follow-up was 5.46 years (range, 4.17-7.33 years). Hazard ratios (99% confidence intervals [CIs]) for prostate cancer were 1.13 (99% CI, 0.95-1.35; n = 473) for vitamin E, 1.04 (99% CI, 0.87-1.24; n = 432) for selenium, and 1.05 (99% CI, 0.88-1.25; n = 437) for selenium + vitamin E vs 1.00 (n = 416) for placebo. There were no significant differences (all P>.15) in any other prespecified cancer end points. There were statistically nonsignificant increased risks of prostate cancer in the vitamin E group (P = .06) and type 2 diabetes mellitus in the selenium group (relative risk, 1.07; 99% CI, 0.94-1.22; P = .16) but not in the selenium + vitamin E group.ConclusionSelenium or vitamin E, alone or in combination at the doses and formulations used, did not prevent prostate cancer in this population of relatively healthy men.Trial registrationclinicaltrials.gov identifier: NCT00006392.

Used national telephone survey data to examine associations between adults' fruit and vegetable consumption and awareness of "5 A Day for Better Health," stage of change, taste preferences, self-efficacy, and perceived benefits, barriers, threats, social support, and norms regarding fruit and vegetable consumption. Strong associations existed among awareness, psychosocial factors, stage of change, and fruit and vegetable consumption. (Contains references.) (SM)