Elevated 4-Aminobiphenyl and 2,6-Dimethylaniline Hemoglobin Adducts and Increased Risk of Bladder Cancer among Lifelong Nonsmokers-The Shanghai Bladder Cancer Study

Background: 4-Aminobiphenyl (ABP) is an established human bladder carcinogen, with tobacco smoke being a major source of human exposure. Other arylamine compounds, including 2,6-dimethylaniline (2,6-DMA), have been implicated as possible human bladder carcinogens. Hemoglobin adducts of 4-ABP and 2,6-DMA are validated biomarkers of exposure to those compounds in humans. Methods: The Shanghai Bladder Cancer Study enrolled 581 incident bladder cancer cases and 604 population controls. Each participant was solicited for his/her history of tobacco use and other lifestyle factors and donation of blood and urine specimens. Red blood cell lysates were used to quantify both hemoglobin adducts of 4-ABP and 2,6-DMA. Urine samples were used to quantify total cotinine. ORs and 95% confidence intervals (CI) for bladder cancer were estimated using unconditional logistic regression methods. Results: Among lifelong nonsmokers, ORs (95% CIs) of bladder cancer for low (below median of positive values) and high versus undetectable levels of 2,6-DMA hemoglobin adducts were 3.87 (1.39-10.75) and 6.90 (3.17-15.02), respectively (P-trend < 0.001). Similarly, among lifelong nonsmokers, ORs (95% CIs) of bladder cancer for third and fourth versus first/second quartiles of 4-ABP hemoglobin adducts was 1.30 (0.76-2.22) and 2.29 (1.23-4.24), respectively (P-trend = 0.009). The two associations were independent of each other. Conclusion: Hemoglobin adducts of 4-ABP and 2,6-DMA were significantly and independently associated with increased bladder cancer risk among lifelong nonsmokers in Shanghai, China. Impact: The findings of the present study in China with previous data in Los Angeles, California strongly implicate arylamines as potential causal agents of human bladder cancer. (C) 2013 AACR.