certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: None.Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.In this prospective study of physical activity and prostate cancer among 49 160 men, vigorous activity was associated with lower risk of lethal and TMPRSS2:ERG-positive disease. Long-term vigorous activity may be beneficial in prevention of lethal prostate cancer and may involve pathways specific to TMPRSS2:ERG-positive disease.

Purpose: Statins are associated with lower risk of aggressive prostate cancer, but lethal prostate cancer is understudied and contributing mechanisms are unclear. We prospectively examined statins and lethal prostate cancer risk in the Health Professionals Follow-up Study (HPFS), tested associations with molecular subtypes, and integrated gene expression profiling to identify putative mechanisms. Experimental Design: Our study included 44,126 men cancer-free in 1990, followed for prostate cancer incidence through 2014, with statin use recorded on biennial questionnaires. We used multivariable Cox regression to examine associations between statins and prostate cancer risk overall, by measures of clinically significant disease, and by ERG and PTEN status. In an exploratory analysis, age-adjusted gene set enrichment analysis identified statin-associated pathways enriched in tumor and adjacent normal prostate tissue. Results: During 24 years of follow-up, 6,305 prostate cancers were diagnosed and 801 (13%) were lethal (metastatic at diagnosis or metastatic/fatal during follow-up). Relative to never/past use, current statin use was inversely associated with risk of lethal prostate cancer [HR, 0.76; 95% confidence interval (CI), 0.60–0.96] but not overall disease. We found a strong inverse association for risk of PTEN-null cancers (HR, 0.40; 95% CI, 0.19–0.87) but not PTEN-intact cancers (HR, 1.18; 95% CI, 0.95–1.48; P heterogeneity = 0.01). Associations did not differ by ERG. Inflammation and immune pathways were enriched in normal prostate tissue of statin ever (n = 10) versus never users (n = 103). Conclusions: Molecular tumor classification identified PTEN and inflammation/immune activation as potential mechanisms linking statins with lower lethal prostate cancer risk. These findings support a potential causal association and could inform selection of relevant biomarkers for statin clinical trials.

No abstract

Background-Seasonal influenza vaccination has been routinely recommended for adults with high-risk conditions. The Advisory Committee on Immunization Practices recommended that persons 25 to 64 years of age with high-risk conditions be one of the initial target groups to receive H1N1 vaccination during the 2009-2010 season.

The largest molecular subtype of primary prostate cancer is defined by the gene fusion. Few studies, however, have investigated etiologic differences by status. Because the fusion is hormone-regulated and a man's hormonal milieu varies by height and obesity status, we hypothesized that both may be differentially associated with risk of -defined disease. Our study included 49,372 men from the prospective Health Professionals Follow-up Study. Participants reported height and weight at baseline in 1986 and updated weight biennially thereafter through 2009. Tumor ERG protein expression (a marker) was immunohistochemically assessed. We used multivariable competing risks models to calculate HRs and 95% confidence intervals (CIs) for the risk of ERG-positive and ERG-negative prostate cancer. During 23 years of follow-up, we identified 5,847 incident prostate cancers, among which 913 were ERG-assayed. Taller height was associated with an increased risk of ERG-positive disease only [per 5 inches HR 1.24; 95% confidence interval (CI), 1.03-1.50; = 0.07]. Higher body mass index (BMI) at baseline (per 5 kg/m HR 0.75; 95% CI, 0.61-0.91; = 0.02) and updated BMI over time (per 5 kg/m HR 0.86; 95% CI, 0.74-1.00; = 0.07) were associated with a reduced risk of ERG-positive disease only. Our results indicate that anthropometrics may be uniquely associated with -positive prostate cancer; taller height may be associated with greater risk, whereas obesity may be associated with lower risk. Our study provides strong rationale for further investigations of other prostate cancer risk factors that may be distinctly associated with subtypes. .