Abstract BACKGROUND: HGPIN shares many phenotypic and genetic traits with PC, and historically, a patient with HGPIN at biopsy was at high-risk for PC at future biopsy. Although obesity and certain medications have been associated with PC risk, no lifestyle or chemoprevention recommendations are available to prevent PC in high-risk men with HGPIN. OBJECTIVE: Determine the prospective association between obesity and medication use for obesity-related comorbidities with the conversion from HGPIN to PC at follow-up. METHODS: Men seeking a prostate biopsy were targeted for recruitment. After consent, we measured weight, height, sitting height, and waist and hip circumferences, and demographics by questionnaire. Pathology charts were reviewed to identify patients with HGPIN and without PC or other suspicious findings. Medication use for diabetes, BPH, high cholesterol, and hypertension at recruitment were extracted from medical charts. There were 105 HGPIN patients with at least one follow-up prostate biopsy and thus with a potential for PC at follow-up. Multivariable logistic regression was used to determine the association between body size and medication use with PC risk, controlling for age at recruitment, number of follow-up biopsies (1, 2, >2), PSA (ng/ml), and prostate size (mls). RESULTS: Average age, PSA level, and prostate size were 65 years, 6.4 ng/ml, and 49 mls, respectively. Median follow-up was 5 years, and 13 patients had more than one follow-up biopsy. During follow-up, 45 men were diagnosed with PC. Increasing waist-hip ratio (WHR) was significantly associated with conversion from HGPIN to PC (OR = 2.26 (1.14, 4.47), p=0.02, per 0.1 increase in WHR). Men with a WHR > 1.00 were 2.7 times more likely to be diagnosed with PC compared to men with a WHR=<1.00 (p=0.02). Waist circumference (WC) was marginally associated with conversion to PC (OR = 1.04 (1.00, 1.08), p=0.05, per cm). BMI, height, and sitting height were not significantly associated with PC. Furthermore, use of statins or anti-hypertensive medications at baseline were marginally significantly associated with a lower PC risk (Statin: OR=0.43 (0.18, 1.06), p=0.06; HTN: OR=0.47 (0.20, 1.09), p=0.08). In contrast, diabetes and BPH medications, or regular aspirin use, were not associated with PC. Strengths include systematic HGPIN evaluation from one pathologist, little patient migration, measured body size, and medical chart data. However, inference is restricted to those HGPIN patients who received a follow-up biopsy. CONCLUSION: Centralized obesity measured as WHR increased the risk of PC among HGPIN patients, while statins and hypertension medications were associated marginally with lower PC risk. The role of hyperlipidemia and statins in PC progression following HGPIN development requires further investigation. Citation Format: Jay H. Fowke, Saundra Motley, Susan Byerly. Prospective association between obesity and statin use with conversion from high-grade prostatic intraepithelial neoplasia (HGPIN) to prostate cancer (PC). [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2175. doi:10.1158/1538-7445.AM2014-2175