Abstract 4647: 4-Aminobiphenyl hemoglobin adducts in relation to risk of bladder cancer among lifelong nonsmokers

Abstract

Abstract Background: 4-aminobiphenyl (4-ABP), a human bladder carcinogen, is known to be present in the general environment besides tobacco smoke. 4-ABP hemoglobin (Hb) adducts is an objective biomarker for exposure to 4-ABP. Studies on 4-ABP Hb adducts and bladder cancer risk among lifelong nonsmokers are sparse. Methods: The Shanghai Bladder Cancer Study enrolled 581 bladder cancer patients (25-74 yr) and 604 healthy controls. Each participant was asked to provide information on tobacco use and other lifestyle factors, and to donate a blood and an overnight urine sample after ingesting 70 mg caffeine. Urine samples were assayed to quantify total cotinine, cytochrome P450 1A2 (CYP1A2) and N-acetyl-transferase 2 (NAT2) phenotype. Peripheral blood components were used to assess glutathione S-transferase M1 (GSTM1) and GSTT1 null versus non-null genotypes (lymphocyte DNA), and 4-ABP Hb adducts (erythrocyte lysate). The present analysis included 158 cases and 210 controls who reported never having used any tobacco products and for whom urinary total cotinine was ≤75 ng/ml. Odds ratios (ORs) and 95% confidence intervals (CIs) for bladder cancer were estimated using unconditional logistic regression methods. Results: The OR of bladder cancer for the top 25th percentile levels of 4-ABP Hb adducts was 1.60 (95% CI 0.97-2.64) relative to below median level. This positive association was confined to women (OR 2.27, 95% CI 1.12-4.59). The ABP-bladder cancer association appeared to be modified by CYP1A2 phenotype and GSTM1 and GSTT1 genotypes, but not by NAT2 phenotype. Compared with below median level of 4-ABP Hb adducts, OR for above median level was 1.78 (95% CI 0.96-3.31) among individuals with above median CYP1A2 index score, while no risk (OR 0.96, 95% CI 0.50-1.85) was seen among those with below median CYP1A2 score. Similarly, high level of 4-ABP Hb adducts was associated with an increased bladder cancer risk among individuals possessing a GSTM1 null genotype (OR 1.63, 95% CI 0.95-2.81) or a GSTT1 null genotype (OR 1.92, 95% CI 1.02-3.61), but not among those possessing a non-null genotype. When all four genetically determined factors – CYP1A2, GSTM1, GSTT1, and NAT2 were combined, high level of 4-ABP Hb adducts was associated with a 78% increased risk (P = 0.048) for individuals possessing 2-4 genetic risk factors whereas no risk was seen for those with 0-1 genetic risk factor. Conclusion: Higher levels of 4-ABP Hb adducts were associated with increased risk of bladder cancer among female lifelong nonsmokers. The genetically determined factors, including CYP1A2 and GST genotypes appear to exert a modifying effect of 4-ABP on bladder carcinogenesis that is unrelated to tobacco use. Our findings emphasize the need to identify the sources of arylamines among non-smoker, given their important role in bladder carcinogenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4647. doi:10.1158/1538-7445.AM2011-4647