Abstract PR-8: Gene-environment interactions between JAZF1 and occupational and neighborhood lead exposure in African American prostate cancer cases

Abstract

Abstract African American men have the highest incidence of prostate cancer in the world and have substantially higher rates of prostate cancer when compared to white men in the U.S. The cause(s) for this race disparity remains elusive. A single nucleotide polymorphism (SNP), rs10486567, in intron 2 of juxtaposed with another zinc finger protein 1 (JAZF1) has been associated with increased risk of prostate cancer in genome-wide association studies (GWAS) and may be key to uncovering reasons for disparities in the disease. JAZF1 is a cysteine-hystidine structured zinc finger protein, a type of protein that has been shown to interact with lead in vitro. Lead is recognized as a probable carcinogen in humans and African American men who are residentially segregated to industrialized urban environments in the U.S. have higher blood lead levels on average compared to white men. In a case-only study of 228 African American men with prostate cancer diagnosed at a large health system in the Detroit Metropolitan area, we assessed gene-environment interactions (GxE) between rs10486567 (CC vs. CT/TT genotype) and two sources of lead exposure. Lifetime occupational lead exposure was determined through industrial hygiene review of extensive face-to-face interviews. Neighborhood lead exposure, defined as the median proportion of census tract housing built before 1950 (≥ 47% vs. <47%), was derived from subjects address at time of diagnosis. Generalized estimating equation (GEE) modeling was used for analyses that included nested census data. In younger African American cases (<62 years of age), we found a significant gene-environment interaction between rs10486567 CC carriers and high occupational-respiratory lead exposure when compared to those with no respiratory lead exposure (OR 2.68, CI 1.05-6.88, p=.04). A significant GxE interaction was also observed between CC carriers and residence in a neighborhood with a large proportion of older housing in all cases and younger cases (all OR 1.92, CI 1.12-3.29, p=.017, younger OR 2.64, CI 1.21-5.73, p=.014, older OR 1.64, CI 0.73-3.70, p=.23). The interaction between rs10486567 and housing remained significant even after adjustment for occupational lead exposure. Combining lead exposure from occupation and neighborhood housing into a four category index showed even stronger interactions between the polymorphism and the highest lead exposed group compared to the lowest exposure group (all OR 3.13, CI 1.22-7.99, p=.017). These findings indicate that lead may be an important risk factor for prostate cancer in carriers of the rs10486567 CC genotype. Future studies of race disparities in prostate cancer should further assess interactions between lead and JAZF1 and lead and other zinc containing proteins. Focusing on genes and polymorphisms identified in GWAS studies might help to identify environmental risk factors for prostate cancer. Citation Information: Cancer Epidemiol Biomarkers Prev 2010;19(10 Suppl):PR-8.