Salas, Lucas A.Villanueva Belmonte, CristinaTajuddin, Salman MuhammadAmaral, André F.S.Fernández, Agustín F.Moore, Lee E.Carrato, AlfredoTardón, AdoninaSerra, ConsolGarcía Closas, ReinaBasagaña Flores, XavierRothman, NathanielSilverman, Debra T.Cantor, Kenneth PKogevinas, ManolisReal, Francisco X.Fraga, Mario F.Malats i Riera, Núria2018-05-112018-05-112014Salas LA, Villanueva CM, Tajuddin SM, Amaral AF, Fernandez AF, Moore LE et al. LINE-1 methylation in granulocyte DNA and trihalomethane exposure is associated with bladder cancer risk. Epigenetics. 2014 Nov;9(11):1532-9. DOI: 10.4161/15592294.2014.9833771559-2294http://hdl.handle.net/10230/34617DNA methylation changes contribute to bladder carcinogenesis. Trihalomethanes (THM), a class of disinfection by-products, are associated with increased urothelial bladder cancer (UBC) risk. THM exposure in animal models produces DNA hypomethylation. We evaluated the relationship of LINE-1 5-methylcytosine levels (LINE-1%5mC) as outcome of long-term THM exposure among controls and as an effect modifier in the association between THM exposure and UBC risk. We used a case-control study of UBC conducted in Spain. We obtained personal lifetime residential THM levels and measured LINE-1%5mC by pyrosequencing in granulocyte DNA from blood samples in 548 incident cases and 559 hospital controls. Two LINE-1%5mC clusters (above and below 64%) were identified through unsupervised hierarchical cluster analysis. The association between THM levels and LINE-1%5mC was evaluated with β regression analyses and logistic regression was used to estimate odds ratios (OR) adjusting for covariables. LINE-1%5mC change between percentiles 75(th) and 25(th) of THM levels was 1.8% (95% confidence interval (CI): 0.1, 3.4%) among controls. THM levels above vs. below the median (26 μg/L) were associated with increased UBC risk, OR = 1.86 (95% CI: 1.25, 2.75), overall and among subjects with low levels of LINE-1%5mC (n = 975), OR = 2.14 (95% CI: 1.39, 3.30), but not associated with UBC risk among subjects' high levels of LINE-1%5mC (n = 162), interaction P = 0.03. Results suggest a positive association between LINE-1%5mC and THM levels among controls, and LINE-1%5mC status may modify the association between UBC risk and THM exposure. Because reverse causation and chance cannot be ruled out, confirmation studies are warranted.application/pdfeng© Taylor & Francis. This is an electronic version of an article published in Salas LA, Villanueva CM, Tajuddin SM, Amaral AF, Fernandez AF, Moore LE et al. LINE-1 methylation in granulocyte DNA and trihalomethane exposure is associated with bladder cancer risk. Epigenetics. 2014 Nov; 9(11): 1532-9. Epigenetics is available online at: www.tandfonline.com (http://dx.doi.org/10.4161/15592294.2014.983377)GranulòcitsADN -- MetilacióBufeta -- Càncerinfo:eu-repo/semantics/articlehttp://dx.doi.org/10.4161/15592294.2014.983377info:eu-repo/semantics/openAccess