Experimental and clinical data suggest that aspirin and other nonsteroidal inflammatory drugs may delay the progression of prostate cancer through inhibition of the COX pathway and its effects on cellular proliferation, apoptosis, and angiogenesis. Epidemiologic data support a reduced risk of prostate cancer incidence with aspirin use, yet no evidence exists about whether aspirin after diagnosis influences progression or survival. We conducted a prospective study of 3,986 participants of the Health Professionals Follow-up Study, with a prostate cancer diagnosis between January 1, 1990, and December 31, 2005. We used Cox proportional hazards regression to evaluate the association between aspirin use after diagnosis and the development of metastases or fatal prostate cancer through January 31, 2008, adjusting for risk factors associated with incidence and mortality in this cohort, prediagnostic aspirin use, Gleason score, tumor-node-metastasis (TNM) stage, and primary treatment. In total, 265 men developed bony or other organ metastases or fatal prostate cancer during the 18 years of follow-up. We observed no association between updated aspirin use after diagnosis and lethal prostate cancer [tablets/week: <2: HR, 1.12; 95% confidence interval (CI), 0.72-1.72; 2-5: HR, 1.05; 95% CI, 0.62-1.80; ≥ 6: HR, 1.08; 95% CI, 0.76-1.54; P(trend) = 0.99]. The results remained unchanged when we examined aspirin use at baseline only (P(trend) = 0.70) or frequency of use (d/wk; P(trend) = 0.35) or limited the outcome to fatal prostate cancer (P(trend) = 0.63). There was no association between aspirin use after a prostate cancer diagnosis and lethal disease in this cohort of prostate cancer survivors.

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.

Purpose

Many prostate cancer survivors experience compromised health-related quality of life (HRQOL) as a result of prostate cancer. We examined relationships between types and intensities of activity and sedentary behavior and prostate cancer-related HRQOL, overall, and by demographic, disease, and treatment characteristics.

Methods

Associations between post-diagnosis activity and sedentary behavior and HRQOL domains (urinary incontinence, urinary irritation/obstruction, bowel, sexual, and vitality/hormonal) were prospectively examined in men diagnosed with non-metastatic prostate cancer in the Health Professionals Follow-up Study (n = 1917) using generalized linear models.

Results

After adjusting for potential confounders, higher duration of total, non-vigorous, and walking activity was associated with higher vitality/hormonal functioning scores (p-trends, <0.0001). Effects were small (d = 0.16-0.20) but approached clinical significance for men in the highest vs. lowest activity categories. Survivors who walked ≥ 90 min/week at a normal pace, or faster, reported higher hormone/vitality scores (p = 0.001) than men walking <90 min at an easy pace. Weightlifting was associated with increased urinary incontinence (p-trend, 0.02). Total activity was associated with higher hormone/vitality functioning in men who were ≥ 5 years post-treatment, had more advanced disease (Gleason score ≥ 7), and had ≥ 1 comorbid condition. No relationships were observed between vigorous activity or sedentary behavior and HRQOL.

Conclusions

Increased duration of non-vigorous activity and walking post-diagnosis was positively associated with better hormone/vitality functioning. Specifically, engaging in ≥ 5 h of non-vigorous activity or ≥ 3 h of walking per week may be beneficial.

Implications for cancer survivors

Encouraging men to engage in non-vigorous activity and walking may be helpful for managing prostate cancer-related HRQOL.

Background

Observational studies suggest potential chemopreventive benefits of statins on prostate cancer outcomes, but data on the impact of postdiagnostic use are sparse.

Methods

We examined the association of postdiagnostic statin use and risk of lethal prostate cancer (metastases or prostate cancer death, N = 242) among 3,949 men diagnosed with localized prostate cancer from the Health Professionals Follow-Up Study between 1992 and 2008 and followed through 2010 (33,302 person years). We used Cox proportional hazards regression models to estimate relative risks and 95% confidence intervals (CI), adjusting for age, time period, time from diagnosis to questionnaire, body mass index, vigorous physical activity, smoking, aspirin use, clinical stage, PSA at diagnosis, Gleason score, primary treatment, and comorbidities.

Results

We found no statistically significant association between postdiagnostic current use of statins or duration of statin usage and the outcome of lethal prostate cancer [N = 242 cases; multivariate HR = 0.97 (95% CI, 0.72-1.31) for current use yes/no; HR = 0.85 (95% CI, 0.59-1.22) for 1 to 5 years of use, 0.96 (95% CI, 0.66-1.38) for 6+ years of use vs. never use].

Conclusions

We observed little evidence that statin usage after diagnosis of localized prostate cancer reduces risk of progression to metastatic disease or prostate cancer-specific death.

Impact

These results do not support statins as a chemopreventive agent for prostate cancer progression.

Importance

Erectile dysfunction, especially in younger men, is an early sign of cardiovascular disease and may decrease quality of life. Men may be motivated to adopt a healthy dietary pattern if it lowers their risk of erectile dysfunction.

Objective

To assess the association between adherence to a diet quality index based on healthy dietary patterns and erectile dysfunction in men.

Design, setting, and participants

This population-based prospective cohort study included men from the Health Professionals Follow-up Study with follow-up from January 1, 1998, through January 1, 2014. Participants included US male health professionals aged 40 to 75 years at enrollment. Men with erectile dysfunction or a diagnosis of myocardial infarction, diabetes, stroke, or genitourinary cancer at baseline were excluded. Analyses were completed in February 2020.

Exposures

A food frequency questionnaire was used to determine nutrient and food intake every 4 years.

Main outcomes and measures

Diet quality was assessed by Mediterranean Diet score and the Alternative Healthy Eating Index 2010 score, with higher scores indicating healthier diet. Dietary index scores were cumulatively updated from 1986 until men developed erectile dysfunction, cardiovascular disease, died, or were lost to follow-up. Incident erectile dysfunction was assessed with questionnaires in 2000, 2004, 2008, and 2012. Hazard ratios (HRs) by prespecified categories or quintiles of dietary index scores were estimated using Cox proportional hazards regression analyses stratified by age.

Results

Among 21 469 men included in analysis, mean (SD) age at baseline was 62 (8.4) years. During a mean (SD) follow-up of 10.8 (5.4) years and 232 522 person-years, there were 968 incident erectile dysfunction cases among men younger than 60 years, 3703 cases among men aged 60 to less than 70 years, and 4793 cases among men aged 70 years or older. Men younger than 60 years and in the highest category of the Mediterranean Diet score had the lowest relative risk of incident erectile dysfunction compared with men in the lowest category (HR, 0.78; 95% CI, 0.66-0.92). Higher Mediterranean diet scores were also inversely associated with incident erectile dysfunction among older men (age 60 to <70 years: HR, 0.82; 95% CI, 0.76-0.89; age ≥70 years: HR, 0.93; 95% CI, 0.86-1.00). Men scoring in the highest quintile of the Alternative Healthy Eating Index 2010 also had a lower risk of incident erectile dysfunction, particularly among men age younger than 60 years (quintile 5 vs quintile 1: HR, 0.78; 95% CI, 0.63-0.97).

Conclusions and relevance

This cohort study found that adherence to healthy dietary patterns was associated with a lower risk for erectile dysfunction, suggesting that a healthy dietary pattern may play a role in maintaining erectile health.

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.

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.

Background

The association between sugar-sweetened beverage (SSB) consumption and colorectal cancer (CRC) risk remains unclear and published data are limited.

Methods

The analytic cohort included 99,798 women, free of cancer at baseline, from the California Teachers Study, a longitudinal cohort comprised of 133,477 female teachers and administrators who were active or recently retired members of the California State Teachers Retirement System in 1995. SSB consumption constituted caloric soft drinks, sweetened bottled waters and teas, and fruit drinks, derived from a self-administered food frequency questionnaire. Consumption was divided into four categories: Rare or never, >rare/never to <1 serving/week, ≥1 serving/week to <1 serving/day, and ≥1 serving/day. CRC endpoints were based on annual linkage with California Cancer Registry, defined as first diagnosis of CRC, and classified following the Surveillance, Epidemiology, and End Results Program coding system. Multivariable-adjusted Cox proportional hazards models were used to generate hazard ratios (HR) and 95% confidence intervals (CI) for assessing the association between SSB consumption and incident CRC.

Results

A total of 1,318 incident CRC cases were identified over 20 years of follow-up (54.5% proximal colon and 45.5% distal colorectum). Compared with rare/never consumers, the multivariable-adjusted HRs (95% CI) were 1.14 (0.86, 1.53) for total CRC; 1.11 (0.73, 1.68) for proximal colon; and 1.22 (0.80, 1.86) for distal colorectum cancers among women consuming ≥ 1 serving/day of SSBs.

Conclusion

SSBs were not significantly associated with CRC risk. The biological effects of high SSB consumption make it important to continue to evaluate whether SSBs are associated with CRC. Additionally, future studies should further assess SSBs in large, racial/ethnically diverse cohorts of males and females, and, if feasible, address changes in SSB consumption over time.

Background

Gut microbial dysbiosis contributes to colorectal cancer (CRC) pathogenesis, possibly mediated in part by increased intestinal permeability to endotoxin lipopolysaccharide (LPS), microbial translocation, and subsequent endotoxemia and inflammation. However, epidemiologic evidence linking circulating markers of microbial translocation with CRC risk is limited.

Methods

We conducted a prospective, nested case-control study of 261 incident CRC cases and 261 controls (matched on age and time of blood draw) among 18,159 men with pre-diagnostic blood specimens in the Health Professionals Follow-Up Study (1993-2009). We examined three complementary markers of microbial translocation and host response to bacteria, including LPS-binding protein (LBP), soluble CD14 (sCD14), and endotoxincore antibody (EndoCAb) immunoglobulin M (IgM), with subsequent risk of CRC. Unconditional logistic regressions were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs).

Findings

Pre-diagnostic circulating levels of sCD14 were associated with a higher risk of incident CRC. Compared to men in the lowest quartile, the multivariable OR was 1.90 (95% CI, 1.13-3.22) for men in the highest quartile (OR _{per standard deviation [SD] increase}, 1.28; 95%CI 1.06-1.53; P_trend = 0.01). This positive association remained similar after adjusting for C-reactive protein, interleukin-6, and soluble tumor necrosis factor receptor-2, and within strata of putative CRC risk factors. We also observed a suggestive inverse association between EndoCAb IgM and risk of CRC (OR _{per SD increase}, 0.84; 95%CI 0.69-1.02; P_trend = 0.09).

Interpretation

Microbial translocation and host response to bacteria, as reflected by sCD14, is associated with risk of incident CRC in men.

Funding

US National Institutes of Health.

Vigorous activity is associated with lower risk of prostate cancer progression, but the biologic mechanisms are unknown. Exercise affects vascularization of tumors in animal models, and small, irregularly shaped vessels in prostate tumors are associated with fatal prostate cancer. We hypothesized that men who engaged in vigorous activity or brisk walking would have larger, more regularly shaped vessels in their prostate tumors. We prospectively examined whether physical activity was associated with prostate tumor microvessel morphology among 571 men in the Health Professionals Follow-up Study using ordinal logistic regression. Vessel size (μm(2)), vessel lumen regularity (perimeter(2)/4 · Π · area), and microvessel density (number/high-powered field) were ascertained in tumor sections stained for endothelial cell marker CD34. Vigorous activity [metabolic equivalent task (MET) ≥ 6], nonvigorous activity (MET < 6), and walking pace were assessed a median of 14 months before diagnosis. Prostate tumors from men who reported a brisk walking pace (3+ mph) had larger, more regularly shaped blood vessels compared with those of men who walked at a less than brisk pace [vessel regularity OR, 1.59; 95% confidence interval (CI), 1.11-2.27; P value, 0.01; vessel size OR, 1.48; 95% CI, 1.04-2.12; P value, 0.03]. Brisk walking was not associated with microvessel density; total vigorous and nonvigorous activities were not associated with vessel size, shape, or number. Brisk walking may be associated with larger, more regularly shaped vessels in prostate tumors. Additional research elucidating the effect of physical activity on prostate tumor biology is needed.