DNA methylation levels and long-term trihalomethane exposure in drinking water: an epigenome-wide association study.

Salas, Lucas A.; Bustamante Pineda, Mariona; González Ruiz, Juan Ramón; Gracia Lavedan, Esther; Moreno, Víctor; Kogevinas, Manolis; Villanueva Belmonte, Cristina

DNA methylation levels and long-term trihalomethane exposure in drinking water: an epigenome-wide association study.

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dc.contributor.author Salas, Lucas A.ca
dc.contributor.author Bustamante Pineda, Marionaca
dc.contributor.author González Ruiz, Juan Ramónca
dc.contributor.author Gracia Lavedan, Estherca
dc.contributor.author Moreno, Víctorca
dc.contributor.author Kogevinas, Manolisca
dc.contributor.author Villanueva Belmonte, Cristinaca
dc.date.accessioned 2015-10-28T09:00:18Z
dc.date.issued 2015
dc.description.abstract Trihalomethanes (THM) are undesired disinfection byproducts (DBPs) formed during water treatment. Mice exposed to DBPs showed global DNA hypomethylation and c-myc and c-jun gene-specific hypomethylation, while evidence of epigenetic effects in humans is scarce. We explored the association between lifetime THM exposure and DNA methylation through an epigenome-wide association study. We selected 138 population-based controls from a case-control study of colorectal cancer conducted in Barcelona, Spain, exposed to average lifetime THM levels ≤85 μg/L vs. >85 μg/L (N = 68 and N = 70, respectively). Mean age of participants was 70 years, and 54% were male. Average lifetime THM level in the exposure groups was 64 and 130 µg/L, respectively. DNA was extracted from whole blood and was bisulphite converted to measure DNA methylation levels using the Illumina HumanMethylation450 BeadChip. Data preprocessing was performed using RnBeads. Methylation was compared between exposure groups using empirical Bayes moderated linear regression for CpG sites and Gaussian kernel for CpG regions. ConsensusPathDB was used for gene set enrichment. Statistically significant differences in methylation between exposure groups was found in 140 CpG sites and 30 gene-related regions, after false discovery rate <0.05 and adjustment for age, sex, methylation first principal component, and blood cell proportion. The annotated genes were localized to several cancer pathways. Among them, 29 CpGs had methylation levels associated with THM levels (|Δβ|≥0.05) located in 11 genes associated with cancer in other studies. Our results suggest that THM exposure may affect DNA methylation in genes related to tumors, including colorectal and bladder cancers. Future confirmation studies are required.ca
dc.description.sponsorship This study was funded by the Spanish Health Ministry (Fondo de Investigaciones Sanitarias–FIS, Instituto de Salud Carlos III, Spain number FIS PI11- 226). Lucas A Salas received a Colciencias PhD Scholarship, Colombia (Grant: 529/2011). Parc de Salut Mar Biobank (MARBiobanc) provided biobanking facilities for to the project. MARBiobanc is supported by Instituto de Salud Carlos III FEDER (RD09/0076/00036).
dc.format.mimetype application/pdfca
dc.identifier.citation Salas LA, Bustamante M, Gonzalez JR, Gracia-Lavedan E, Moreno V, Kogevinas M. et al. DNA methylation levels and long-term trihalomethane exposure in drinking water: an epigenome-wide association study. Epigenetics. 2015; 10(7): 650-61. DOI: 10.1080/15592294.2015.1057672.ca
dc.identifier.doi http://dx.doi.org/10.1080/15592294.2015.1057672
dc.identifier.issn 1559-2294
dc.identifier.uri http://hdl.handle.net/10230/24919
dc.language.iso engca
dc.publisher Taylor & Francisca
dc.relation.ispartof Epigenetics. 2015;10(7):650-61
dc.rights © Taylor & Francis. This is an electronic version of an article published in Salas LA, Bustamante M, Gonzalez JR, Gracia-Lavedan E, Moreno V, Kogevinas M. et al. DNA methylation levels and long-term trihalomethane exposure in drinking water: an epigenome-wide association study. Epigenetics. 2015;10(7):650-61. Epigenetics is avalaible online at http://dx.doi.org/10.1080/15592294.2015.1057672.ca
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.subject.other Aigua potable -- Abastament -- Aspectes sanitarisca
dc.subject.other Trihalometans -- Toxicologiaca
dc.title DNA methylation levels and long-term trihalomethane exposure in drinking water: an epigenome-wide association study.ca
dc.type info:eu-repo/semantics/articleca
dc.type.version info:eu-repo/semantics/acceptedVersionca

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