Abstract B106: Alcohol consumption and TMPRSS2:ERG gene fusion in prostate cancer
Authors: Lin Shih-Wen , Stark Jennifer R. , Meyer Mara , Penney Kathryn L. , Hendrickson Whitney , Kasperzyk Julie L. , Ma Jing , Sesso Howard D. , Flavin Richard J. , Giovannucci Edward , Stampfer Meir , Loda Massimo , Mucci Lorelei A. 
Published: May 2012

Abstract
Objectives: The novel TMPRSS2:ERG gene fusion is a common somatic event in prostate cancer that in some studies is linked with a more aggressive disease phenotype. TMPRSS2 is strongly regulated by androgens, and our preliminary data suggests that TMPRSS2:ERG-positive tumor cells may be more responsive to IGF signaling pathways. Alcohol consumption has been shown to be associated with a number of hormones in men, including higher total and free testosterone levels, and lower circulating IGF-1. Thus, this study aims to determine whether increased alcohol consumption levels are associated with the presence of TMPRSS2:ERG-negative prostate cancer.
Methods: We evaluated the association of baseline alcohol consumption with the risk of developing TMPRSS2:ERG gene fusion-positive and -negative prostate cancer nested among 16,601 men in the Physicians' Health Study I, 1982–2008. Alcohol consumption levels were defined as low (0–3 drinks/month), moderate (1–6 drinks/week), and daily (1+ drinks/day). We characterized the TMPRSS2:ERG fusion using fluorescent in situ hybridization assay on tissue microarrays constructed from paraffin-embedded prostate cancer specimens (N=317). We applied Cox proportional hazards regression, separately for fusion-positive and -negative prostate cancer, to compare the effects of alcohol use on the risk of developing prostate cancer, controlling for baseline characteristics and dietary factors.
Results: Of 317 cases, 42.6% were fusion positive. The risk of developing TMPRSS2:ERG-positive prostate cancer tended to decrease with each increasing level of alcohol consumption (p-trend 0.30). Compared to men with low consumption, the hazard ratio was 0.90 (95% Confidence Interval [CI] 0.59–1.37) for men with moderate intake and 0.75 (95% CI 0.44–1.28) for men with daily intake. The risk of developing TMPRSS2:ERG-negative prostate cancer increased with each increasing level of alcohol consumption (p-trend 0.03). Compared to men with low consumption, the hazard ratio was 1.02 (95% CI 0.69–1.49) for men with moderate intake and 1.58 (95% CI 1.04–2.41) for men with daily intake.
Conclusions: Prostate cancer is a heterogeneous disease that may be defined by molecular subtypes such as the TMPRSS2:ERG fusion. The regulation of TMPRSS2:ERG by androgens and possibly IGF suggests that the epidemiology may differ for fusion-positive and -negative prostate cancer. Results from our study suggest that alcohol consumption is more likely related to the development of TMPRSS2:ERG-negative prostate cancer tumors rather than TMPRSS2:ERG-positive prostate cancer tumors. Understanding external modifiable risk factors such as diet and lifestyle will help emphasize the importance of individual behavior in the prevention of prostate cancer development and progression.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):B106.