The Prostate 68:281^286 (2008) Finasteride, Prostate Cancer, and Weight Gain: Evidence for Genetic or Environmental FactorsThat Affect Cancer Outcomes During FinasterideTreatment YoonJu Song, 1 Catherine Tangen, 1 Phyllis Goodman, 1 Howard L. Parnes, 2 M. Scott Lucia, 3 Ian M. Thompson, 4 and Alan R. Kristal 1,5 * ,{ 1 Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle,Washington 2 Division of Cancer Prevention, National Cancer Institute, Bethesda, Maryland 3 Department of Pathology,University of Colorado Health Science Center, Denver,Colorado 4 Department of Urology,The University of Texas Health Sciences Center at San Antonio, San Antonio,Texas 5 Department of Epidemiology, School of Public Health and Community Medicine,University of Washington, Seattle,Washington OBJECTIVE. Finasteride affects both prostate cancer risk and body weight. We examined whether, during 7 years of finasteride treatment, the magnitude of weight change was associated with the diagnosis of no, low-, or high-grade cancer. METHODS. Data are from 10,057 participants in Prostate Cancer Prevention Trial (PCPT), a randomized trial of finasteride for primary prevention of prostate cancer. Mixed linear models were used to calculate percentage change in weight per year, controlling for demographic and health-related covariates. RESULTS. Weight gain was modestly lower in the finasteride compared to placebo arms (0.14 vs. 0.16% per year, P < 0.025). On the placebo arm, there was no association of weight gain with cancer outcomes. In the finasteride arm, annual weight gain among men without cancer was 0.14%, and among men with cancer ranged from 0.01% for those diagnosed with high-grade cancer following a clinical indication for biopsy (P ¼ 0.03 vs. no cancer) to 0.25% among men diagnosed with low-grade cancer at the end of the trial with no indication for biopsy (P ¼ 0.002 vs. no cancer). CONCLUSIONS. In finasteride-treated men, there are significant associations between prostate cancer outcomes and weight gain, which suggest that there are common or closely related individual-level factors that affect both treatment responses. This supports the hypothesis that there are genetic characteristics and/or environmental exposures that affect finasteride outcomes which, when identified, could be used to target men most likely to benefit from finasteride treatment. Prostate 68: 281 – 286, 2008. # 2007 Wiley-Liss, Inc. KEY WORDS: prostate cancer; weight gain; finasteride INTRODUCTION The Prostate Cancer Prevention Trial (PCPT) was a randomized, placebo-controlled clinical trial testing the drug finasteride for primary prevention of prostate cancer [1]. Finasteride, a 5-a-reductase inhibitor, blocks the conversion of testosterone (T) to its active metab- olite dihydrotestosterone (DHT) in human prostate. { Member and Associate Head Grant sponsor: National Institutes of Health; Grant numbers: CA37429, CA108964. *Correspondence to: Alan R. Kristal, DPH, Cancer Prevention Program, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, M4-B402, P.O. Box 19024, Seattle, WA 98109-1024. E-mail: akristal@fhcrc.org Received 24 April 2007; Accepted 18 June 2007 DOI 10.1002/pros.20637 Published online 28 December 2007 in Wiley InterScience (www.interscience.wiley.com). ß 2007 Wiley-Liss, Inc.