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

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 casecontrol study of colorectal cancer conducted in Barcelona, Spain, exposed to average lifetime THM levels 85 mg/L vs. >85 mg/L (N D 68 and N D 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 mg/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 (|Db| 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.

Maternal Swimming Pool Exposure during Pregnancy in Relation to Birth Outcomes and Cord Blood DNA Methylation among Private Well Users

“…They found reduced cord blood Alu and LINE-1 methylation in those with higher blood bromoform levels at their first prenatal visit although this was not statistically significant. This is consistent with prior work on chronic exposure to trihalomethanes through drinking water indicating changes in LINE-1 methylation of granulocytes among healthy subjects and bladder cancer patients and epigenome wide changes in blood DNA methylation after adjusting for blood cell composition among healthy subjects (Salas et al, 2015(Salas et al, , 2014. Two studies in healthy volunteers have examined gene expression changes after a short-term exposure to swimming pools, suggesting small and potentially reversible changes in swimmers (Espín-Pérez et al, 2018;Salas et al, 2017).…”

“…colorectal, kidney and breast cancer), alterations in the sperm quality, and disruption of the menstrual cycle (Villanueva et al, 2015). In mechanistic studies, swimming pool exposure has been associated with changes in gene expression, changes in micronuclei, DNA damage, and epigenetic alterations (Espín-Pérez et al, 2018;Kogevinas et al, 2010;Salas et al, 2017Salas et al, , 2015Villanueva et al, 2015;. Composition of DBPs, and in turn their toxicity, differs in drinking water and pools.…”

Long-term exposure to trihalomethanes in drinking water and breast cancer in the Spanish multicase-control study on cancer (MCC-SPAIN)

“…Epigenetic changes in DNA methylation have also been suggested as another potential mechanism of DBP toxicity (Salas et al 2015). DBPs are not considered important endocrine disruptors, but very little toxicological evidence is available (Klinefelter et al 2004).…”

Genetic and epigenetic methylation defects and implication of the ERMN gene in autism spectrum disorders

“…Additional methylation data from 91 controls (males of a wide age range) were obtained from the Center for Research in Environmental Epidemiology (CREAL) and the Bellvitge Institute for Biomedical Research (IDIBELL), 25 , 26 as well as from 656 controls (males and females of European ancestry aged from 19 to 101 years) available through GEO (GSE40279). All 757 control samples were obtained from whole blood, except for 5 from cord blood.…”