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Title: Biological and statistical approaches for modeling exposure to specific trihalomethanes and bladder cancer risk.
Authors: Salas LA,  Cantor KP,  Tardon A,  Serra C,  Carrato A,  Garcia-Closas R,  Rothman N,  Malats N,  Silverman D,  Kogevinas M,  Villanueva CM
Journal: Am J Epidemiol
Date: 2013 Aug 15
Branches: NEB, OEEB
PubMed ID: 23648803
PMC ID: PMC3736753
Abstract: Lifetime exposure to trihalomethanes (THM) has been associated with increased risk of bladder cancer. We explored methods of analyzing bladder cancer risk associated with 4 THM (chloroform, bromodichloromethane, dibromochloromethane, and bromoform) as surrogates for disinfection by-product (DBP) mixtures in a case-control study in Spain (1998-2001). Lifetime average concentrations of THM in the households of 686 incident bladder cancer cases and 750 matched hospital-based controls were calculated. Several exposure metrics were modeled through conditional logistic regression, including the following analyses: total THM (μg/L), cytotoxicity-weighted sum of total THM (pmol/L), 4 THM in separate models, 4 THM in 1 model, chloroform and the sum of brominated THM in 1 model, and a principal-components analysis. THM composition, concentrations, and correlations varied between areas. The model for total THM was stable and showed increasing dose-response trends. Models for separate THM provided unstable estimates and inconsistent dose-response relationships. Risk estimation for specific THM is hampered by the varying composition of the mixture, correlation between species, and imprecision of historical estimates. Total THM (μg/L) provided a proxy measure of DBPs that yielded the strongest dose-response relationship with bladder cancer risk. A variety of metrics and statistical approaches should be used to evaluate this association in other settings.