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2026-01-11

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cc-by (c) Moratalla Navarro, Ferran et al., 2026
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/228965

Genome-wide interaction analysis of long-term trihalomethane exposure in drinking water and colorectal cancer risk in a Spanish Multicenter Case-Control Study (MCC-Spain)

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Recurs relacionat

https://doi.org/10.1016/j.envint.2026.110059

Resum

We conducted a genome-wide interaction analysis between long-term exposure to trihalomethanes in drinking water and colorectal cancer (CRC) risk in a multicenter case-control study in Spain, including 1037 CRC cases and 2100 controls. Exposure categories were estimated based on sex-specific median and quartile values of total trihalomethanes (TTHM), chloroform (CHCl3), and brominated trihalomethanes (Br-THMs) among controls. In addition, TTHM exposure was assessed relative to the WHO guideline thresholds. Gene-environment interaction models were computed with the GxEScanR package. To explore biological plausibility, relevant results were inspected in search of expression quantitative trait loci (eQTLs) in two independent resources: BarcUVaSeq and the Genome Tissue Expression (GTEx) v8. Finally, we searched the Comparative Toxicogenomics Database to identify candidate genes previously linked to trihalomethane exposure, retrieved their eQTLs, and evaluated gene-environment interactions with TTHM levels. We found three variants that modulated CRC risk in relation to CHCl3 and TTHM exposure: rs77985109 near LRRC8B, chr15:28997737 near WHAMMP2, and rs7890183 near MAGEB2. Two additional variants were specifically found for women and one for rectal cancer. Functional assessment suggested a regulatory role of rs77985109 in LRRC8B expression. Moreover, eQTL analysis of candidate genes revealed an additional variant associated with CCL2 which could modulate CRC risk under different TTHM exposure levels. The present study identified novel loci potentially influencing CRC susceptibility under THM exposure, highlighting the importance of integrating environmental and genetic data to better understand environmental driven cancer risks. Further research is needed to confirm these results and clarify underlying mechanisms.

Matèries

Aigua potable, Contaminants orgànics de l'aigua, Càncer colorectal

Matèries (anglès)

Drinking water, Organic water pollutants, Colorectal cancer

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Col·leccions

Articles publicats en revistes (Ciències Clíniques)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Articles publicats en revistes (Institut de Recerca en Sistemes Complexos (UBICS))
Articles publicats en revistes (Nutrició, Ciències de l'Alimentació i Gastronomia)

Citació

MORATALLA NAVARRO, Ferran, et al. Genome-wide interaction analysis of long-term trihalomethane exposure in drinking water and colorectal cancer risk in a Spanish Multicenter Case-Control Study (MCC-Spain). Environment International. 2026. Vol. 207, num. 110059. ISSN 0160-4120. [consulted: 3 of August of 2026]. Available at: https://hdl.handle.net/2445/228965

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