Abstract
PURPOSE: A single nucleotide polymorphism, rs10486567, in JAZF1 has consistently been associated with increased risk of prostate cancer. The physical interaction of zinc finger proteins, such as JAZF1, with heavy metals may play a role in carcinogenesis. This study assessed potential gene-environment statistical interactions (G×E) between rs10486567 and heavy metals in prostate cancer. METHODS: In a case-only study of 228 African American prostate cancer cases, G×E between rs10486567 and sources of cadmium and lead (Pb) were assessed. Unconditional logistic regression was used to estimate interaction odds ratios (IORs), and generalized estimating equations were used for models containing nested data. Case-control validation of IORs was performed, using 82 controls frequency matched to cases on age-race. RESULTS: Among cases, a potential G×E interaction was observed between rs10486567 CC genotype and living in a Census tract with a high proportion of housing built before 1950, a proxy for household Pb exposure, when compared to CT or TT carriers (OR 1.81; 95% CI 1.04-3.16; p = 0.036). A stronger G×E interaction was observed when both housing and occupational Pb exposure were taken into account (OR 2.62; 95% CI 1.03-6.68; p = 0.04). Case-control stratified analyses showed the odds of being a CC carrier were higher in cases compared to controls among men living in areas with older housing (OR 2.03; CI 0.99-4.19; p = 0.05) or having high occupational Pb exposure (OR 2.50; CI 1.01-6.18; p = 0.05). CONCLUSIONS: In African American men, the association between JAZF1 rs10486567 and prostate cancer may be modified by exposure to heavy metals such as Pb.