ASPO Abstracts
Interactive Effects of Obesity and Androgen Receptor Polymorphisms on Prostate Cancer Outcomes
Category: Molecular Epidemiology & Environment, Early Detection & Risk Prediction
Conference Year: 2018
Abstract Body:
Purpose: Obesity and the androgen receptor (AR) gene have been implicated as drivers in the progression of prostate cancer (PCa). The goal of this study was to examine the interactive effects of obesity and AR on PCa outcomes. Methods: Our sample included 1486 PCa patients. Obesity was defined as body mass index 30kg/m2. We studied key polymorphisms in AR activation: CAG ( 21 vs. < 21 repeats) and GGC (< 17 vs. 17 repeats). High tumor stage was defined as T3/T4. High tumor grade was defined Gleason score 7. Biochemical failure was defined as PSA 0.2 ng/ml after definitive treatment. We fit independent logistic regression models for each genotype adjusted for age and race on tumor stage and grade. Cox regression models were used to evaluate time-to-biochemical failure adjusted for age, race and grade. A p-value <0.05 was considered significant. Results: The median age of the sample was 60 and median BMI was 28.Twenty-two percent of the sample was African American. Thirty-five percent of the sample carried < 21 CAG repeats and 80% carried 17 GGC repeats on AR. The prevalence of advanced tumor stage was 28%, advanced tumor grade was 46%, and biochemical recurrence was 19% with a median follow-up time of 34 months. There were no significant interactions between genotype and obese status in modelling tumor grade. However, multivariable analyses suggested that obesity and AR GGC 17 repeats associations were not additive in predicting advanced stage PCa at diagnosis (interaction OR=0.34, p=0.025) and that, compared to non-obese men with < 17 AR GGC repeats, obese men with < 17 AR GGC repeats experienced about a 3-fold increase in odds of advanced stage PCa (OR = 3.22, 95% CI=1.36-7.61). Also, obesity and AR CAG < 21 repeats associations were not additive in predicting biochemical failure risk (interaction HR=2.20, p=0.049).Compared to non-obese men with 21 AR CAG repeats, non-obese men with < 21 AR CAG repeats experienced about a 34% reduction in risk of biochemical failure (HR = 0.66, 95% CI=0.43-1.00). Conclusions: We observed interactions between obesity and AR related to PCa progression. It appears that associations between PCa outcomes and AR are contingent upon patient obesity status.
Keywords: Prostate cancer Androgen Receptor Gene Obesity