title: Biological and statistical approaches for modeling exposure to specific trihalomethanes and bladder cancer risk.
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.
authors: Centre for Research in Environmental Epidemiology, Barcelona, Spain.
authors: Lucas A
authors: LA
authors: Salas
authors: Kenneth P
authors: KP
authors: Cantor
authors: Adonina
authors: A
authors: Tardon
authors: Consol
authors: C
authors: Serra
authors: Alfredo
authors: A
authors: Carrato
authors: Reina
authors: R
authors: Garcia-Closas
authors: Nathaniel
authors: N
authors: Rothman
authors: Núria
authors: N
authors: Malats
authors: Debra
authors: D
authors: Silverman
authors: Manolis
authors: M
authors: Kogevinas
authors: Cristina M
authors: CM
authors: Villanueva
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D045424:Complex Mixtures / Q000633:toxicity; D004781:Environmental Exposure / Q000009:adverse effects*; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D015337:Multicenter Studies as Topic; D025341:Principal Component Analysis / Q000379:methods; D018570:Risk Assessment; D013030:Spain; D022882:Trihalomethanes / Q000633:toxicity*; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced*; D055815:Young Adult
chemical_list: D045424:Complex Mixtures; D022882:Trihalomethanes
keywords: Spain; chloroform; complex mixtures; logistic models; principal-components analysis; trihalomethanes; urinary bladder neoplasms
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