Journal
AMERICAN JOURNAL OF EPIDEMIOLOGY
Volume 181, Issue 9, Pages 706-713Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/aje/kwu344
Keywords
body mass index; obesity; prostate cancer; TMPRSS2:ERG gene fusion
Categories
Funding
- National Cancer Institute [R01 CA056678, R01 CA092579, P50 CA097186]
- Prostate Cancer Foundation
- Fred Hutchinson Cancer Research Center
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The T2E gene fusion, formed by fusion of the transmembrane protease, serine 2, gene (TMPRSS2) with the erythroblast transformation-specific (ETS)-related gene (ERG), is found in approximately 50% of prostate cancers and may characterize distinct molecular subtypes of prostate cancer with different etiologies. We investigated the relationship between body mass index (BMI; weight (kg)/height (m)(2)) and prostate cancer risk by T2E status. Study participants were residents of King County, Washington, recruited for 2 population-based case-control studies conducted in 1993-1996 and 2002-2005. Tumor T2E status was determined for 563 prostate cancer patients who underwent radical prostatectomy. Information on weight, height, and covariables was obtained through in-person interviews. We performed polytomous logistic regression to calculate odds ratios and 95% confidence intervals for T2E-positive and -negative prostate cancer. Comparing the highest BMI quartile with the lowest, inverse associations were observed between recent (>= 29.7 vs. <24.5: odds ratio = 0.66, 95% confidence interval: 0.45, 0.97) and maximum (>= 31.8 vs. <25.9: odds ratio = 0.69, 95% confidence interval: 0.47, 1.02) BMI and the risk of T2E-positive prostate cancer. No significant associations were seen for men with T2E-negative tumors. This study provides evidence that obesity is specifically associated with reduced risk of developing androgen-responsive T2E fusion-positive tumors. The altered steroid hormone profile in obese men may contribute to this inverse association.
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