Abstract B20: Polymorphism analyses in specific xenobiotic-metabolizing genes of Hispanic farmworkers from the San Joaquin Valley with hormone-dependent cancer

Abstract

Abstract Organochlorines (OC) are a common class of pesticides known as endocrine disruptors in humans. OC pesticides are known to modify the effects of estrogen and testosterone and may act as agonists or antagonists or have mixed effects in the microenvironment of tissues. The pathway to pesticide (xenobiotic) elimination from the body is a multi-step process resulting in excretion of contaminants through the urine or bile. The first step involves oxidation which is primarily carried out by the Phase I enzyme family, cytochrome P450 (CYP), and is typically an activating reaction creating a more polar byproduct. The second step involves conjugation with an endogenous ligand through a Phase II enzyme family, glutathione-S-transferase (GST), and is typically a detoxifying reaction. The goals of this study have been to determine the association between exposure to OC pesticides and risk of a hormone-dependent cancer (breast or prostate) in the Hispanic population of the intensely agricultural San Joaquin Valley of California. Our case-control study involves the use of DNA samples consented from 42 Hispanic female participants and 180 Hispanic male participants and assesses single nucleotide polymorphisms (SNPs) in select xenobiotic-metabolizing genes utilizing three different molecular strategies. For female samples, we found no association between the GSTM1 null polymorphism and breast cancer risk in this sample (O.R. = 0.99, 95% CI=0.28, 3.51), but did find a doubling in breast cancer risk among those women who carried the null polymorphism for GSTT1 (O.R. = 2.21, 95% CI=0.39, 12.63). In females, two CYP1B1 polymorphisms (codon 119 Ala/Ser and codon 432 Val/Leu) were also genotyped. While no association in breast cancer risk for codon 119 (O.R. = 0.77, 95% CI=0.14, 3.70) was found, we did find elevated risk of breast cancer (O.R. 2.33, 95% CI= 0.64, 8.54) at codon 432 (Val>Leu) suggesting that women carrying the Val CYP1B1 allele had higher risk than those women with the Leu/Leu genotype. Due to the small sample population, Odds Ratios are deemed statistically unstable and thus one must be prudent in drawing firm conclusions. Analyses of male samples are ongoing. This study indicates that it is feasible to identify, trace, consent and recruit female and male Hispanic participants in the San Joaquin Valley of California who have recently been diagnosed with breast cancer or prostate cancer for future interventional studies. Citation Format: Yesenia Ibarra, Malika Sahni, Kathryn Patterson, Jessica Borba, Jason A. Bush, Paul K. Mills. Polymorphism analyses in specific xenobiotic-metabolizing genes of Hispanic farmworkers from the San Joaquin Valley with hormone-dependent cancer. [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 B20. doi:10.1158/1538-7755.DISP13-B20