Polymorphisms in GSTT1, GSTZ1, AND CYP2E1, disinfection by-products, and risk of bladder cancer in Spain

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• dc.contributor.author Cantor, Kenneth Pca
• dc.contributor.author Villanueva Belmonte, Cristinaca
• dc.contributor.author Silverman, Debra T.ca
• dc.contributor.author Figueroa, Jonine D.ca
• dc.contributor.author Real, Francisco X.ca
• dc.contributor.author García Closas, Montserratca
• dc.contributor.author Malats i Riera, Núriaca
• dc.contributor.author Chanock, Stephen J.ca
• dc.contributor.author Yeager, Meredithca
• dc.contributor.author Tardón, Adoninaca
• dc.contributor.author García Closas, Reinaca
• dc.contributor.author Serra, Consolca
• dc.contributor.author Carrato, Alfredoca
• dc.contributor.author Castaño Vinyals, Gemmaca
• dc.contributor.author Samanic, Claudineca
• dc.contributor.author Rothman, Nathanielca
• dc.contributor.author Kogevinas, Manolisca
• dc.date.accessioned 2015-04-08T10:14:42Z
• dc.date.available 2015-04-08T10:14:42Z
• dc.date.issued 2010ca
• dc.description.abstract Background: Bladder cancer has been linked with long-term exposure to disinfection by-products (DBPs) in drinking water.Objectives: In this study we investigated the combined influence of DBP exposure and polymorphisms in glutathione S-transferase (GSTT1, GSTZ1) and cytochrome P450 (CYP2E1) genes in the metabolic pathways of selected by-products on bladder cancer in a hospital-based case–control study in Spain. Methods: Average exposures to trihalomethanes (THMs; a surrogate for DBPs) from 15 years of age were estimated for each subject based on residential history and information on municipal water sources among 680 cases and 714 controls. We estimated effects of THMs and GSTT1, GSTZ1, and CYP2E1 polymorphisms on bladder cancer using adjusted logistic regression models with and without interaction terms. Results: THM exposure was positively associated with bladder cancer: adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were 1.2 (0.8–1.8), 1.8 (1.1–2.9), and 1.8 (0.9–3.5) for THM quartiles 2, 3, and 4, respectively, relative to quartile 1. Associations between THMs and bladder cancer were stronger among subjects who were GSTT1 +/+ or +/– versus GSTT1 null (pinteraction = 0.021), GSTZ1 rs1046428 CT/TT versus CC (pinteraction = 0.018), or CYP2E1 rs2031920 CC versus CT/TT (pinteraction = 0.035). Among the 195 cases and 192 controls with high-risk forms of GSTT1 and GSTZ1, the ORs for quartiles 2, 3, and 4 of THMs were 1.5 (0.7–3.5), 3.4 (1.4–8.2), and 5.9 (1.8–19.0), respectively. Conclusions: Polymorphisms in key metabolizing enzymes modified DBP-associated bladder cancer risk. The consistency of these findings with experimental observations of GSTT1, GSTZ1, and CYP2E1 activity strengthens the hypothesis that DBPs cause bladder cancer and suggests possible mechanisms as well as the classes of compounds likely to be implicated.en
• dc.description.sponsorship This work was funded by the Intramural Research Program of the National Institutes of Health, National Cancer Institute (N02-CP-11015), the Fondo de Investigación Sanitaria (00/0745, G03/174, G03/160, C03/09, and C03/90), and the Instituto de Salud Carlos III, Spanish Health Ministry (CP06/00341)en
• dc.format.mimetype application/pdfca
• dc.identifier.citation Cantor KP, Villanueva CM, Silverman DT, Figueroa JD, Real FX, Garcia-Closas M et al. Polymorphisms in GSTT1, GSTZ1, AND CYP2E1, disinfection by-products, and risk of bladder cancer in Spain. Environmental Health Perspectives. 2010;118(11):1545-50. DOI: 10.1289/ehp.1002206ca
• dc.identifier.doi http://dx.doi.org/10.1289/ehp.1002206
• dc.identifier.issn 0091-6765ca
• dc.identifier.uri http://hdl.handle.net/10230/23352
• dc.language.iso engca
• dc.publisher National Institute of Environmental Health Sciences (NIEHS)ca
• dc.relation.ispartof Environmental Health Perspectives. 2010;118(11):1545-50
• dc.rights Reproduced with permission from Environmental Health Perspectivesca
• dc.rights.accessRights info:eu-repo/semantics/openAccessca
• dc.subject.keyword Bladder canceren
• dc.subject.keyword CYP2E1en
• dc.subject.keyword Disinfection by-productsen
• dc.subject.keyword Drinking wateren
• dc.subject.keyword GSTT1en
• dc.subject.keyword GSTZ1en
• dc.subject.keyword Trihalomethanesen
• dc.subject.other Bufeta -- Tumorsca
• dc.subject.other Aigua -- Depuracióca
• dc.title Polymorphisms in GSTT1, GSTZ1, AND CYP2E1, disinfection by-products, and risk of bladder cancer in Spainen
• dc.type info:eu-repo/semantics/articleca
• dc.type.version info:eu-repo/semantics/publishedVersionca