LINE-1 methylation in granulocyte DNA and trihalomethane exposure is associated with bladder cancer risk

Salas, Lucas A.; Villanueva Belmonte, Cristina; Tajuddin, Salman Muhammad; Amaral, André F.S.; Fernández, Agustín F.; Moore, Lee E.; Carrato, Alfredo; Tardón, Adonina; Serra, Consol; García Closas, Reina; Basagaña Flores, Xavier; Rothman, Nathaniel; Silverman, Debra T.; Cantor, Kenneth P; Kogevinas, Manolis; Real, Francisco X.; Fraga, Mario F.; Malats i Riera, Núria

LINE-1 methylation in granulocyte DNA and trihalomethane exposure is associated with bladder cancer risk

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dc.contributor.author Salas, Lucas A.ca
dc.contributor.author Villanueva Belmonte, Cristinaca
dc.contributor.author Tajuddin, Salman Muhammadca
dc.contributor.author Amaral, André F.S.ca
dc.contributor.author Fernández, Agustín F.ca
dc.contributor.author Moore, Lee E.ca
dc.contributor.author Carrato, Alfredoca
dc.contributor.author Tardón, Adoninaca
dc.contributor.author Serra, Consolca
dc.contributor.author García Closas, Reinaca
dc.contributor.author Basagaña Flores, Xavierca
dc.contributor.author Rothman, Nathanielca
dc.contributor.author Silverman, Debra T.ca
dc.contributor.author Cantor, Kenneth Pca
dc.contributor.author Kogevinas, Manolisca
dc.contributor.author Real, Francisco X.ca
dc.contributor.author Fraga, Mario F.ca
dc.contributor.author Malats i Riera, Núriaca
dc.date.accessioned 2018-05-11T09:18:59Z
dc.date.available 2018-05-11T09:18:59Z
dc.date.issued 2014
dc.description.abstract DNA 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.
dc.description.sponsorship This study was partially supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics (Contract NCI NO2-CP-11015); the Spanish Health Ministry (Fondo de Investigaciones Sanitarias–FIS, Instituto de Salud Carlos III, Spain 00/0745, ISIII-GO3/174, PI080533, PI051436, PI061614, PI09–02102, and PI11/00226) and the European Union (BMH4–98–3243); Red Temática de Investigación Cooperativa en Cáncer- RD12/0036/0050-RTICC; USA-NIH-RO1-CA089715; a postdoctoral fellowship awarded to AFSA from the Fundación Científica de la AECC; Fundació Marató TV3. The work was partially supported by the Association for International Cancer Research (AICR, #09–0780, including a PhD scholarship awarded to S.M.T.). The current analyses were supported by a Colciencias PhD Scholarship, Colombia (Grant: 529/2011 to L.A.S.). This work was also supported by grants from the Instituto de Salud Carlos III FEDER, (PI11/00226)
dc.format.mimetype application/pdf
dc.identifier.citation 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. DOI: 10.4161/15592294.2014.983377
dc.identifier.doi http://dx.doi.org/10.4161/15592294.2014.983377
dc.identifier.issn 1559-2294
dc.identifier.uri http://hdl.handle.net/10230/34617
dc.language.iso eng
dc.publisher Taylor & Francis (Routledge)ca
dc.relation.ispartof Epigenetics. 2014 Nov;9(11):1532-9
dc.rights © 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)
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.rights.uri http://creativecommons.org/licenses/by-nc/3.0/
dc.subject.other Granulòcits
dc.subject.other ADN -- Metilació
dc.subject.other Bufeta -- Càncer
dc.title LINE-1 methylation in granulocyte DNA and trihalomethane exposure is associated with bladder cancer riskca
dc.type info:eu-repo/semantics/article
dc.type.version info:eu-repo/semantics/publishedVersion

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