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)

Moratalla Navarro, Ferran; Obón Santacana, Mireia; Rius Sansalvador, Blanca; Guinó, Elisabet; Moragas, Núria; Donat Vargas, Carolina; Fernández de Larrea-Baz, Nerea; Molina Barceló, Ana; Guevara, Marcela; Morón-Duran, Francisco D; Dierssen Sotos, Trinidad; Tardón, Adonina; Castaño-Vinyals, Gemma; Cabrera Castro, Natalia; Molina, Antonio J.; Aizpurua Atxega, Amaia; Morales Suárez Varela, María M.; Martín, Vicente; Fernández Navarro, Pablo; Villanueva, Cristina M.; Moreno Aguado, Víctor

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)

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 a...

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Authors:	Moratalla Navarro, Ferran, Obón Santacana, Mireia, Rius Sansalvador, Blanca, Guinó, Elisabet, Moragas, Núria, Donat Vargas, Carolina, Fernández de Larrea-Baz, Nerea, Molina Barceló, Ana, Guevara, Marcela, Morón-Duran, Francisco D, Dierssen Sotos, Trinidad, Tardón, Adonina, Castaño-Vinyals, Gemma, Cabrera Castro, Natalia, Molina, Antonio J., Aizpurua Atxega, Amaia, Morales Suárez Varela, María M., Martín, Vicente, Fernández Navarro, Pablo, Villanueva, Cristina M., Moreno Aguado, Víctor
Format:	article
Status:	Published version
Publication Date:	2026
Country:	España
Institution:	Universidad de Barcelona
Repository:	Dipòsit Digital de la UB
OAI Identifier:	oai:dnet:ubarcelona__::360c159c0f19f6264b48037c6f3e2875
Online Access:	https://hdl.handle.net/2445/228965
Access Level:	Open access
Keyword:	Aigua potable Contaminants orgànics de l'aigua Càncer colorectal Drinking water Organic water pollutants Colorectal cancer

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spelling	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)Moratalla Navarro, FerranObón Santacana, MireiaRius Sansalvador, BlancaGuinó, ElisabetMoragas, NúriaDonat Vargas, CarolinaFernández de Larrea-Baz, NereaMolina Barceló, AnaGuevara, MarcelaMorón-Duran, Francisco DDierssen Sotos, TrinidadTardón, AdoninaCastaño-Vinyals, GemmaCabrera Castro, NataliaMolina, Antonio J.Aizpurua Atxega, AmaiaMorales Suárez Varela, María M.Martín, VicenteFernández Navarro, PabloVillanueva, Cristina M.Moreno Aguado, VíctorAigua potableContaminants orgànics de l'aiguaCàncer colorectalDrinking waterOrganic water pollutantsColorectal cancerWe 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.Elsevier Ltd.2026info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/228965Articles publicats en revistes (Ciències Clíniques)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1016/j.envint.2026.110059Environment International, 2026, vol. 207, p. 110059https://doi.org/10.1016/j.envint.2026.110059cc-by (c) Moratalla Navarro, Ferran et al., 2026https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:dnet:ubarcelona__::360c159c0f19f6264b48037c6f3e28752026-05-27T06:46:51Z
dc.title.none.fl_str_mv	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)
title	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)
spellingShingle	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) Moratalla Navarro, Ferran Aigua potable Contaminants orgànics de l'aigua Càncer colorectal Drinking water Organic water pollutants Colorectal cancer
title_short	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)
title_full	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)
title_fullStr	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)
title_full_unstemmed	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)
title_sort	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)
dc.creator.none.fl_str_mv	Moratalla Navarro, Ferran Obón Santacana, Mireia Rius Sansalvador, Blanca Guinó, Elisabet Moragas, Núria Donat Vargas, Carolina Fernández de Larrea-Baz, Nerea Molina Barceló, Ana Guevara, Marcela Morón-Duran, Francisco D Dierssen Sotos, Trinidad Tardón, Adonina Castaño-Vinyals, Gemma Cabrera Castro, Natalia Molina, Antonio J. Aizpurua Atxega, Amaia Morales Suárez Varela, María M. Martín, Vicente Fernández Navarro, Pablo Villanueva, Cristina M. Moreno Aguado, Víctor
author	Moratalla Navarro, Ferran
author_facet	Moratalla Navarro, Ferran Obón Santacana, Mireia Rius Sansalvador, Blanca Guinó, Elisabet Moragas, Núria Donat Vargas, Carolina Fernández de Larrea-Baz, Nerea Molina Barceló, Ana Guevara, Marcela Morón-Duran, Francisco D Dierssen Sotos, Trinidad Tardón, Adonina Castaño-Vinyals, Gemma Cabrera Castro, Natalia Molina, Antonio J. Aizpurua Atxega, Amaia Morales Suárez Varela, María M. Martín, Vicente Fernández Navarro, Pablo Villanueva, Cristina M. Moreno Aguado, Víctor
author_role	author
author2	Obón Santacana, Mireia Rius Sansalvador, Blanca Guinó, Elisabet Moragas, Núria Donat Vargas, Carolina Fernández de Larrea-Baz, Nerea Molina Barceló, Ana Guevara, Marcela Morón-Duran, Francisco D Dierssen Sotos, Trinidad Tardón, Adonina Castaño-Vinyals, Gemma Cabrera Castro, Natalia Molina, Antonio J. Aizpurua Atxega, Amaia Morales Suárez Varela, María M. Martín, Vicente Fernández Navarro, Pablo Villanueva, Cristina M. Moreno Aguado, Víctor
author2_role	author author author author author author author author author author author author author author author author author author author author
dc.subject.none.fl_str_mv	Aigua potable Contaminants orgànics de l'aigua Càncer colorectal Drinking water Organic water pollutants Colorectal cancer
topic	Aigua potable Contaminants orgànics de l'aigua Càncer colorectal Drinking water Organic water pollutants Colorectal cancer
description	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.
publishDate	2026
dc.date.none.fl_str_mv	2026
dc.type.none.fl_str_mv	info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion
format	article
status_str	publishedVersion
dc.identifier.none.fl_str_mv	https://hdl.handle.net/2445/228965
url	https://hdl.handle.net/2445/228965
dc.language.none.fl_str_mv	Inglés
language_invalid_str_mv	Inglés
dc.relation.none.fl_str_mv	Reproducció del document publicat a: https://doi.org/10.1016/j.envint.2026.110059 Environment International, 2026, vol. 207, p. 110059 https://doi.org/10.1016/j.envint.2026.110059
dc.rights.none.fl_str_mv	cc-by (c) Moratalla Navarro, Ferran et al., 2026 https://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess
rights_invalid_str_mv	cc-by (c) Moratalla Navarro, Ferran et al., 2026 https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv	openAccess
dc.format.none.fl_str_mv	application/pdf
dc.publisher.none.fl_str_mv	Elsevier Ltd.
publisher.none.fl_str_mv	Elsevier Ltd.
dc.source.none.fl_str_mv	Articles publicats en revistes (Ciències Clíniques) reponame:Dipòsit Digital de la UB instname:Universidad de Barcelona
instname_str	Universidad de Barcelona
reponame_str	Dipòsit Digital de la UB
collection	Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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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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