Physical activity and prostate gene expression in men with low-risk prostate cancer.

PURPOSE: Vigorous physical activity after diagnosis of localized prostate cancer may reduce the risk of disease progression and prostate cancer-specific mortality. The molecular mechanisms by which physical activity may exert protective effects in the prostate remain unknown. METHODS: We examined the associations between self-reported physical activity and gene expression patterns in morphologically normal prostate tissue of 71 men with low-risk prostate cancer on active surveillance. Differential gene expression, gene set, and pathway analyses were conducted comparing dichotomous groups defined by type, intensity, and amount of physical activity reported. RESULTS: Cell cycling and DNA repair pathways were up-regulated in men who participated in ≥ 3 h/week vigorous activity compared with men who did not. In addition, canonical pathways involved in cell signaling and metabolism, the cellular effects of sildenafil (Viagra), and the Nrf2-mediated oxidative stress response were modulated in men who reported ≥ 3 h/week of vigorous activity. Differential expression analysis at the individual gene level revealed modest differences between men who performed vigorous activity for ≥ 3 h/week and those who did not. There were no differences in prostate gene expression in comparisons with exercise groupings that did not consider both duration and intensity of activity. CONCLUSIONS: Prostate gene expression and pathway analyses revealed sets of transcripts that may be modulated in normal prostate tissue by participating in ≥ 3 h/week of vigorous activity after diagnosis of low-risk prostate cancer. These findings suggest potential biological mechanisms by which vigorous activity may reduce risk of prostate cancer progression and warrant further study and validation.

Impact of folate intake on prostate cancer recurrence following definitive therapy: data from CaPSURE™.

PURPOSE: A randomized, placebo controlled clinical trial of folic acid supplementation for the chemoprevention of colorectal adenoma revealed an increased incidence of prostate cancer in the treatment group. Limited data exist on postdiagnostic folate/folic acid intake and the risk of prostate cancer progression. We prospectively examined the association between postdiagnostic folate consumption and the risk of prostate cancer recurrence after radical prostatectomy, external beam radiation therapy and brachytherapy. MATERIALS AND METHODS: This study was done in 1,153 men treated with radical prostatectomy, external beam radiation therapy and brachytherapy who had clinical stage T1-T2c prostate adenocarcinoma and participated in the CaPSURE Diet and Lifestyle substudy by completing the semiquantitative Food Frequency Questionnaire in 2004 to 2005. We used Cox proportional hazards regression to analyze the association between folate intake and prostate cancer progression. RESULTS: Prostate cancer progressed in 101 men (8.76%) during a mean 34-month followup. After multivariate adjustment we observed no evidence of an association of the intake of total folate, dietary folate or dietary folate equivalents with prostate cancer recurrence. On secondary analysis by treatment after radical prostatectomy patients in the lowest decile of dietary folate intake had a 2.6-fold increase in the risk of recurrence (HR 2.56, 95% CI 1.23-5.29, p = 0.01). In patients treated with external beam radiation and brachytherapy we observed no evidence of an association between prostate cancer progression and increased folate intake. CONCLUSIONS: Results suggest that the consumption of foods and multivitamins that contain folate is not associated with prostate cancer progression after definitive treatment.

Antioxidant and vitamin E transport genes and risk of high-grade prostate cancer and prostate cancer recurrence.

BACKGROUND: Observational studies suggest an inverse association between vitamin E and risk of prostate cancer, particularly aggressive tumors. However, three large randomized controlled trials have reported conflicting results. Thus, we examined circulating vitamin E and vitamin E-related genes in relation to risk of high-grade prostate cancer and prostate cancer recurrence among men initially diagnosed with clinically organ-confined disease. METHODS: We measured circulating α- and γ-tocopherol and genotyped 30 SNPs in SOD1, SOD2, SOD3, TTPA, and SEC14L2 among 573 men with organ-confined prostate cancer who underwent radical prostatectomy. We examined associations between circulating vitamin E, genotypes, and risk of high-grade prostate cancer (Gleason grade ≥ 8 or 7 with primary score ≥ 4; n = 117) using logistic regression, and risk of recurrence (56 events; 3.7 years median follow-up) using Cox proportional hazards regression. RESULTS: Circulating γ-tocopherol was associated with an increased risk of high-grade prostate cancer (Q4 v. Q1 odds ratio [OR] = 1.87; 95% confidence intervals [CI]: 0.97-3.58; P trend =0.02). The less common allele in SOD3 rs699473 was associated with an increased risk of high-grade disease (T > C: OR = 1.40, 95% CI: 1.04-1.89). Two independent SNPs in SOD1 were inversely associated with prostate cancer recurrence in additive models (rs17884057 hazard ratio [HR] = 0.49, 95%CI: 0.25-0.96; rs9967983 HR = 0.62, 95% CI: 0.40-0.95). CONCLUSIONS: Among men with clinically organ-confined prostate cancer, genetic variation in SOD may be associated with risk of high-grade disease at diagnosis and disease recurrence. Circulating γ-tocopherol levels may also be associated with an increased risk of high-grade disease at diagnosis.

Vegetable and fruit intake after diagnosis and risk of prostate cancer progression.

Cruciferous vegetables, tomato sauce and legumes have been associated with reduced risk of incident advanced prostate cancer. In vitro and animal studies suggest these foods may inhibit progression of prostate cancer, but there are limited data in men. Therefore, we prospectively examined whether intake of total vegetables, and specifically cruciferous vegetables, tomato sauce and legumes, after diagnosis reduce risk of prostate cancer progression among 1,560 men diagnosed with non-metastatic prostate cancer and participating in the Cancer of the Prostate Strategic Urologic Research Endeavor, a United States prostate cancer registry. As a secondary analysis, we also examined other vegetable subgroups, total fruit and subgroups of fruits. The participants were diagnosed primarily at community-based clinics and followed from 2004 to 2009. We assessed vegetable and fruit intake via a semi-quantitative food frequency questionnaire, and ascertained prostate cancer outcomes via urologist report and medical records. We observed 134 events of progression (53 biochemical recurrences, 71 secondary treatments likely due to recurrence, 6 bone metastases and 4 prostate cancer deaths) during 3,171 person-years. Men in the fourth quartile of post-diagnostic cruciferous vegetable intake had a statistically significant 59% decreased risk of prostate cancer progression compared to men in the lowest quartile (hazard ratio (HR): 0.41; 95% confidence interval (CI): 0.22, 0.76; p-trend: 0.003). No other vegetable or fruit group was statistically significantly associated with risk of prostate cancer progression. In conclusion, cruciferous vegetable intake after diagnosis may reduce risk of prostate cancer progression.

Mediterranean diet and prostate cancer risk and mortality in the Health Professionals Follow-up Study.

BACKGROUND: Prostate cancer (PCa) mortality rates are lower in the Mediterranean countries compared with northern Europe. Although specific components of the Mediterranean diet (Med-Diet) may influence PCa risk, few studies have assessed the traditional Med-Diet pattern with the risk of incident advanced or lethal PCa or with disease progression among men diagnosed with nonmetastatic PCa. OBJECTIVE: To determine whether the traditional Med-Diet pattern is associated with risk of incident advanced or lethal PCa and with PCa-specific and overall mortality among men with PCa. DESIGN, SETTING, AND PARTICIPANTS: We prospectively followed 47 867 men in the Health Professionals Follow-up Study followed from 1986 to 2010. The case-only analysis included 4538 men diagnosed with nonmetastatic PCa, followed from diagnosis to lethal outcome or to January 2010. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We used Cox proportional hazards models to examine traditional and alternative Med-Diet scores in relation to PCa incidence outcomes (advanced and lethal disease). In a case-only survival analysis, we examined postdiagnostic Med-Diet and risk of lethal (metastases or PCa death) and fatal PCa as well as overall mortality among men diagnosed with nonmetastatic disease. RESULTS AND LIMITATIONS: Between 1986 and 2010, 6220 PCa cases were confirmed. The Med-Diet was not associated with risk of advanced or lethal PCa. In the case-only analysis, there was no association between the Med-Diet after diagnosis and risk of lethal or fatal PCa. However, there was a 22% lower risk of overall mortality (hazard ratio: 0.78; 95% confidence interval, 0.67-0.90; p(trend)=0.0007) among men with greater adherence to the Med-Diet after PCa diagnosis. We found similar associations for the alternative score. CONCLUSIONS: A higher Med-Diet score was not associated with risk of advanced PCa or disease progression. Greater adherence to the Med-Diet after diagnosis of nonmetastatic PCa was associated with lower overall mortality.

Fat intake after diagnosis and risk of lethal prostate cancer and all-cause mortality.

IMPORTANCE: Nearly 2.5 million men currently live with prostate cancer in the United States, yet little is known about the association between diet after diagnosis and prostate cancer progression and overall mortality. OBJECTIVE: To examine postdiagnostic fat intake in relation to lethal prostate cancer and all-cause mortality. DESIGN, SETTING, AND PARTICIPANTS: Prospective study of 4577 men with nonmetastatic prostate cancer in the Health Professionals Follow-up Study (1986-2010). EXPOSURES: Postdiagnostic intake of saturated, monounsaturated, polyunsaturated, trans, animal, and vegetable fat. MAIN OUTCOMES AND MEASURES: Lethal prostate cancer (distant metastases or prostate cancer-specific death) and all-cause mortality. RESULTS: We observed 315 events of lethal prostate cancer and 1064 deaths (median follow-up, 8.4 years). Crude rates per 1000 person-years for lethal prostate cancer were as follows (highest vs lowest quintile of fat intake): 7.6 vs 7.3 for saturated, 6.4 vs 7.2 for monounsaturated, 5.8 vs 8.2 for polyunsaturated, 8.7 vs 6.1 for trans, 8.3 vs 5.7 for animal, and 4.7 vs 8.7 for vegetable fat. For all-cause mortality, the rates were 28.4 vs 21.4 for saturated, 20.0 vs 23.7 for monounsaturated, 17.1 vs 29.4 for polyunsaturated, 32.4 vs 17.1 for trans, 32.0 vs 17.2 for animal, and 15.4 vs 32.7 for vegetable fat. Replacing 10% of energy intake from carbohydrate with vegetable fat was associated with a lower risk of lethal prostate cancer (hazard ratio [HR], 0.71; 95% CI, 0.51-0.98; P = .04) and all-cause mortality (HR, 0.74; 95% CI, 0.61-0.88; P = .001). No other fats were associated with lethal prostate cancer. Saturated and trans fats after diagnosis (replacing 5% and 1% of energy from carbohydrate, respectively) were associated with higher all-cause mortality (HR, 1.30 [95% CI, 1.05-1.60; P = .02] and 1.25 [95% CI, 1.05-1.49; P = .01], respectively). CONCLUSIONS AND RELEVANCE: Among men with nonmetastatic prostate cancer, replacing carbohydrates and animal fat with vegetable fat may reduce the risk of all-cause mortality. The potential benefit of vegetable fat for prostate cancer-specific outcomes merits further research.

Choline intake and risk of lethal prostate cancer: incidence and survival.

BACKGROUND: Meat, milk, and eggs have been inconsistently associated with the risk of advanced prostate cancer. These foods are sources of choline-a nutrient that may affect prostate cancer progression through cell membrane function and one-carbon metabolism. No study has examined dietary choline and the risk of lethal prostate cancer. OBJECTIVE: Our objective was to examine whether dietary choline, choline-containing compounds, and betaine (a choline metabolite) increase the risk of lethal prostate cancer. DESIGN: We prospectively examined the intake of these nutrients and the risk of lethal prostate cancer among 47,896 men in the Health Professionals Follow-Up Study. In a case-only survival analysis, we examined the postdiagnostic intake of these nutrients and the risk of lethal prostate cancer among 4282 men with an initial diagnosis of nonmetastatic disease during follow-up. Diet was assessed with a validated questionnaire 6 times during 22 y of follow-up. RESULTS: In the incidence analysis, we observed 695 lethal prostate cancers during 879,627 person-years. Men in the highest quintile of choline intake had a 70% increased risk of lethal prostate cancer (HR: 1.70; 95% CI: 1.18, 2.45; P-trend = 0.005). In the case-only survival analysis, we observed 271 lethal cases during 33,679 person-years. Postdiagnostic choline intake was not statistically significantly associated with the risk of lethal prostate cancer (HR for quintile 5 compared with quintile 1: 1.69; 95% CI: 0.93, 3.09; P-trend = 0.20). CONCLUSION: Of the 47,896 men in our study population, choline intake was associated with an increased risk of lethal prostate cancer.

Milk and dairy consumption among men with prostate cancer and risk of metastases and prostate cancer death.

BACKGROUND: Whether milk and dairy intake after a prostate cancer diagnosis is associated with a poorer prognosis is unknown. We investigated postdiagnostic milk and dairy intake in relation to risk of lethal prostate cancer (metastases and prostate cancer death) among participants in the Health Professionals Follow-Up Study. METHODS: The cohort consisted of 3,918 men diagnosed with apparently localized prostate cancer between 1986 and 2006, and followed to 2008. Data on milk and dairy intake were available from repeated questionnaires. We used Cox proportional hazards models to calculate HRs and 95% CIs of the association between postdiagnostic milk and dairy intake and prostate cancer outcomes. RESULTS: We ascertained 229 prostate cancer deaths and an additional 69 metastases during follow-up. In multivariate analysis, total milk and dairy intakes after diagnosis were not associated with a greater risk of lethal prostate cancer. Men with the highest versus lowest intake of whole milk were at an increased risk of progression (HR = 2.15, 95% CI: 1.28-3.60; P(trend) < 0.01). Men in the highest versus lowest quintile of low-fat dairy intake were at a decreased risk of progression (HR = 0.62; 95% CI: 0.40-0.95; P(trend) = 0.07). CONCLUSIONS: With the exception of whole milk, our results suggest that milk and dairy intake after a prostate cancer diagnosis is not associated with an increased risk of lethal prostate cancer. IMPACT: This is the first larger prospective study investigating the relation between postdiagnostic milk and dairy intake and risk of lethal prostate cancer.

Physical activity after diagnosis and risk of prostate cancer progression: data from the cancer of the prostate strategic urologic research endeavor.

Vigorous activity after diagnosis was recently reported to be inversely associated with prostate cancer-specific mortality. However, men with metastatic disease may decrease their activity due to their disease; thus, a causal interpretation is uncertain. We therefore prospectively examined vigorous activity and brisk walking after diagnosis in relation to risk of prostate cancer progression, an outcome less susceptible to reverse causation, among 1,455 men diagnosed with clinically localized prostate cancer. Cox proportional hazards regression was used to examine vigorous activity, nonvigorous activity, walking duration, and walking pace after diagnosis and risk of prostate cancer progression. We observed 117 events (45 biochemical recurrences, 66 secondary treatments, 3 bone metastases, 3 prostate cancer deaths) during 2,750 person-years. Walking accounted for nearly half of all activity. Men who walked briskly for 3 h/wk or more had a 57% lower rate of progression than men who walked at an easy pace for less than 3 h/wk (HR = 0.43; 95% CI: 0.21-0.91; P = 0.03). Walking pace was associated with decreased risk of progression independent of duration (HR brisk vs. easy pace = 0.52; 95% CI: 0.29-0.91; P(trend) = 0.01). Few men engaged in vigorous activity, but there was a suggestive inverse association (HR ≥3 h/wk vs. none = 0.63; 95% CI: 0.32-1.23; P(trend) = 0.17). Walking duration and total nonvigorous activity were not associated with risk of progression independent of pace or vigorous activity, respectively. Brisk walking after diagnosis may inhibit or delay prostate cancer progression among men diagnosed with clinically localized prostate cancer.

Egg, red meat, and poultry intake and risk of lethal prostate cancer in the prostate-specific antigen-era: incidence and survival.

Red and processed meat may increase risk of advanced prostate cancer. Data on postdiagnostic diet and prostate cancer are sparse, but postdiagnostic intake of poultry with skin and eggs may increase risk of disease progression. Therefore, we prospectively examined total, unprocessed, and processed red meat, poultry, and eggs in relation to risk of lethal prostate cancer (e.g., men without cancer at baseline who developed distant organ metastases or died from prostate cancer during follow-up) among 27,607 men followed from 1994 to 2008. We also conducted a case-only survival analysis to examine postdiagnostic consumption of these foods and risk of lethal prostate cancer among the 3,127 men initially diagnosed with nonmetastatic prostate cancer during follow-up. In the incidence analysis, we observed 199 events during 306,715 person-years. Men who consumed 2.5 or more eggs per week had an 81% increased risk of lethal prostate cancer compared with men who consumed less than 0.5 eggs per week (HR: 1.81; 95% CI: 1.13-2.89; P(trend): 0.01). In the case-only survival analysis, we observed 123 events during 19,354 person-years. There were suggestive, but not statistically significant, positive associations between postdiagnostic poultry (HR ≥ 3.5 vs. <1.5 servings per week: 1.69; 95% CI: 0.96-2.99; P(trend): 0.07) and postdiagnostic processed red meat (HR ≥ 3 vs. <0.5 servings per week: 1.45; 95% CI: 0.73-2.87; P(trend): 0.08) and risk of progression of localized prostate cancer to lethal disease. In conclusion, consumption of eggs may increase risk of developing a lethal form of prostate cancer among healthy men.

Intakes of meat, fish, poultry, and eggs and risk of prostate cancer progression.

BACKGROUND: Processed meat and fish have been shown to be associated with the risk of advanced prostate cancer, but few studies have examined diet after prostate cancer diagnosis and risk of its progression. OBJECTIVE: We examined the association between postdiagnostic consumption of processed and unprocessed red meat, fish, poultry, and eggs and the risk of prostate cancer recurrence or progression. DESIGN: We conducted a prospective study in 1294 men with prostate cancer, without recurrence or progression as of 2004-2005, who were participating in the Cancer of the Prostate Strategic Urologic Research Endeavor and who were followed for an average of 2 y. RESULTS: We observed 127 events (prostate cancer death or metastases, elevated prostate-specific antigen concentration, or secondary treatment) during 2610 person-years. Intakes of processed and unprocessed red meat, fish, total poultry, and skinless poultry were not associated with prostate cancer recurrence or progression. Greater consumption of eggs and poultry with skin was associated with 2-fold increases in risk in a comparison of extreme quantiles: eggs [hazard ratio (HR): 2.02; 95% CI: 1.10, 3.72; P for trend = 0.05] and poultry with skin (HR: 2.26; 95% CI: 1.36, 3.76; P for trend = 0.003). An interaction was observed between prognostic risk at diagnosis and poultry. Men with high prognostic risk and a high poultry intake had a 4-fold increased risk of recurrence or progression compared with men with low/intermediate prognostic risk and a low poultry intake (P for interaction = 0.003). CONCLUSIONS: Our results suggest that the postdiagnostic consumption of processed or unprocessed red meat, fish, or skinless poultry is not associated with prostate cancer recurrence or progression, whereas consumption of eggs and poultry with skin may increase the risk.