Abstract B49: Androgen receptor CAG repeat length association with prostate cancer risk in obese and non-obese African American men

Abstract

Abstract Background. Prostate cancer (PCa) racial disparity is likely to be multifactorial, involving the individual's genotype, the environment and their interaction. The trinucleotide (CAG)(n) repeat polymorphism in exon 1 of the androgen receptor (AR) gene regulates AR activity, with longer alleles conferring reduced activity. Significant interethnic variations in the allele frequencies of the AR (CAG)(n) polymorphism have been reported. We investigated the association between the AR CAG(n) repeat length and PCa risk in African American (AA) and Non-Hispanic White (NHW) men. We further explored if this association varied by body mass index (BMI) in the two races. Methods. We tested DNA samples from 259 (136 cases and 123 controls) AA and 269 (147 cases and 142 controls) NHW men, matched by age, Gleason score and PSA. The CAG repeat region was PCR amplified, and the PCR fragments were analyzed using the Beckman Coulter CEQ8000 DNA sequencer to establish the repeat length. Associations between repeats and PCa risk were evaluated using unconditional logistic regression to estimate odds ratios (OR) and 95% confidence intervals (95%CI) for each race. Repeats were categorized using the median (22 repeats) as a cutpoint. Results. AA men with longer AR CAG repeats (≥22) had a statistically significantly increased PCa risk, compared to AA men with shorter (<22) repeats (OR=1.81; 95%CI=1.05-3.13; P=0.034). The association was further evident among obese AA men (BMI≥30) (OR=3.12; 95%CI=1.12-8.73; P=0.03), but not in non-obese AA men (BMI<30) (OR=1.43; 95%CI=0.73-2.77; P=0.30). No associations were observed between short or long AR CAG repeats and PCa risk among NHW men, regardless of BMI status. Conclusions. Our results suggest that PCa risk may be increased among AA men with longer AR CAG repeats (≥22), especially obese (BMI≥30) AA men. The data provide evidence for ethnic differences in androgenic pathway activity and androgen sensitivity which may contribute to PCa disparity. Citation Format: Ganna Chornokur, Ernest K. Amankwah, Jong Y. Park, Catherine M. Phelan, Julio Powsang, Nagi B. Kumar. Androgen receptor CAG repeat length association with prostate cancer risk in obese and non-obese African American men. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr B49. doi:10.1158/1538-7755.DISP13-B49