[1]Cancer Prevention Institute of California,Fremont,United States
[2]University of Pittsburgh, Department of Pharmaceutical Sciences,Pittsburgh,United States
[3]Renji Hospital, Department of Epidemiology,Shanghai,China
[4]University of Pittsburgh Cancer Institute, Division of Cancer Control and Population Sciences,Pittsburgh,United States
[5]Keck School of Medicine of USC, Department of Preventive Medicine,Los Angeles,United States
[6]UCSD Medical Center, Moores Cancer Center,San Diego,United States
[7]Keck School of Medicine of USC, Department of Obstetrics and Gynecology,Los Angeles,United States
[8]University of Southern California, Department of Preventive Medicine,Los Angeles,United States
[9]University of Southern California/Norris Comprehensive Cancer Center,Los Angeles,United States
[10]Fred Hutchinson Cancer Research Center, the Dept. of Med. Epid. and Biostatistics,Seattle,United States
[11]Medical Center of Fudan University, Department of Epidemiology,Shanghai,China
[12]University of Southern California/Norris Comprehensive Cancer Center, Department of Preventive Medicine,Los Angeles,United States
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 (Ptrend < 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 (Ptrend = 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. Cancer Epidemiol Biomarkers Prev; 22(5); 937-45. © 2013 AACR.
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