Abstract B52: Polymorphisms in the metabolism-related genes and obesity may explain prostate cancer disparity in African American men.

Background. Prostate cancer (PCa) racial disparity is likely to be multifactorial, involving the individual's genotype, the environment and their interaction. We investigated the association between selected functional polymorphisms in the metabolism-related genes and the risk of PCa in African American/ Black and Non-Hispanic White men. We further explored if these associations varied by body mass index (BMI) in the two races.

Methods. DNA samples from 259 (136 cases and 123 controls) Black and 269 (147 cases and 142 controls) White men, matched by age, Gleason score and PSA were genotyped for 10 selected single nucleotide polymorphisms (SNPs) in 7 metabolism related genes using the TaqMan PCR. The dominant, recessive and additive age-adjusted unconditional logistic regression models were fitted for all men combined, for each race and stratified by BMI, height and smoking habits within each race.

Results. Three SNPs showed statistically significant associations with PCa. In Black men: rs7501939 (OR=2.42; CI 1.31-4.47; p=0.0046) and rs4430796 (OR=0.57; CI 0.34-0.97; p=0.0383), both in the HNF1B/ TCF2 gene and associated with diabetes. In White men: rs4962416 (OR=1.52; CI 1.02-2.26; p=0.0384) in the CTBP2 gene. In addition, BMI in Black men (OR=1.06; CI 1.008-1.114; p=0.022), and height in White men (OR=0.92; CI 0.85-0.99; p=0.0434) showed significant associations. Interestingly, rs7501939 in the HNF1B gene was associated with PCa exclusively in obese Black men (OR=2.14; CI 1.2-3.8; p=0.0103).

Conclusions. Our results suggest that polymorphisms in the metabolism related genes may be involved in PCa disparity, possibly through the mechanism of obesity-related hormonal shift and disrupted androgen signaling. We are planning a well-powered study to test this hypothesis.

Citation Format: Ganna Chornokur, Ernest Amankwah, Jong Park, Catherine Phelan, Nagi Kumar. Polymorphisms in the metabolism-related genes and obesity may explain prostate cancer disparity in African American men. [abstract]. In: Proceedings of the Fifth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2012 Oct 27-30; San Diego, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(10 Suppl):Abstract nr B52.