AlkylanilineHemoglobin Adducts and Risk of NonSmoking-Related Bladder Cancer
Authors: Jinping Gan1; Paul L. Skipper2; Manuela Gago-Dominguez3; Kazuko Arakawa2; Ronald K. Ross2; Mimi C. Yu1; Steven R. Tannenbaum3
Source: Journal of the National Cancer Institute, Volume 96, Number 19, 6 October 2004 , pp. 1425-1431(7)
Publisher: Oxford University Press
Abstract:
Background: Some members of the arylamine family of compounds, specifically 4-aminobiphenyl (ABP), 2-naphthylamine, and benzidine, are established human bladder carcinogens. Cigarette smoking and use of permanent hair dye contribute substantially to current arylamine exposure. Low levels of 4-ABP exposure have been associated with nonsmoking-related bladder cancer. Other arylamine compounds coming from as yet unidentified environmental sources may also be human bladder carcinogens. Methods: We conducted a population-based casecontrol study in Los Angeles County, California, involving 298 case subjects with bladder cancer and 308 control subjects, who were matched on age, sex, race/ethnicity, and neighborhood of residence. In-person interviews provided information on tobacco smoking and other potential risk factors for bladder cancer. To assess arylamine exposure, levels of arylaminehemoglobin adducts of nine selected alkylanilines (2,3-dimethylaniline [2,3-DMA], 2,4-DMA, 2,5-DMA, 2,6-DMA, 3,4-DMA, 3,5-DMA, 2-ethylaniline [2-EA], 3-EA, 4-EA) were measured in peripheral blood collected from study subjects. Analysis of covariance and conditional logistic regression methods were used to analyze the relationship between arylaminehemoglobin adducts and bladder cancer risk. All statistical tests were two-sided. Results: Levels of all arylaminehemoglobin adducts, with the exception of 2,6-DMA, were higher in smokers than in nonsmokers, and levels of all arylaminehemoglobin adducts were higher in case subjects than in control subjects. Arylaminehemoglobin adducts of 2,6-DMA, 3,5-DMA, and 3-EA were all independently, statistically significantly (all P<.001) associated with bladder cancer risk after adjusting for cigarette smoking at the time of blood collection, lifetime smoking history, and other potential risk factors. These adducts were also independently associated with bladder cancer risk when only nonsmokers at time of blood draw were considered (highest quartile versus lowest quartile: 2,6-DMA, relative risk [RR] of bladder cancer = 8.1, 95% confidence interval [CI] = 3.6 to 18.0; 3,5-DMA, RR = 2.7, 95% CI = 1.2 to 6.0; 3-EA, RR = 4.3, 95% CI = 1.6 to 11.6). Conclusions: Diverse arylamine exposures are strongly associated with bladder cancer risk among nonsmokers. Because arylamines may account for a substantial proportion of bladder cancers among the general population, identification of environmental sources of these compounds is needed.Document Type: Research article
DOI: 10.1093/jnci/djh274
Affiliations: 1: Affiliations of authors: Biological Engineering Division, Massachusetts Institute of Technology, Cambridge, MA (JG, PLS, SRT); Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles (MGD, KA, R 2: Affiliations of authors: Biological Engineering Division, Massachusetts Institute of Technology, Cambridge, MA (JG, PLS, SRT); Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles (MGD, KA, R 3: Affiliations of authors: Biological Engineering Division, Massachusetts Institute of Technology, Cambridge, MA (JG, PLS, SRT); Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles (MGD, KA, R

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