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

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...

Descripción completa

Detalles Bibliográficos
Autores:	Moratalla-Navarro, Ferrán, Obón-Santacana, Mireia, Rius-Sansalvador, Blanca, Guinó, Elisabet, Moragas, Núria, Donat-Vargas, Carolina, Fernández de Larrea-Baz, Nerea, Molina-Barceló, Ana, Guevara, Marcela, Morón-Durán, Francisco D., Dierssen Sotos, Trinidad, Tardón, Adonina, Castaño-Vinyals, Gemma, Cabrera-Castro, Natalia, Molina, Antonio José, Aizpurua, Amaia, Morales-Suárez-Varela, María M., Martín, Vicente, Fernández-Navarro, Pablo, Villanueva, Cristina M.
Tipo de recurso:	artículo
Fecha de publicación:	2026
País:	España
Institución:	Universidad de Cantabria (UC)
Repositorio:	UCrea Repositorio Abierto de la Universidad de Cantabria
Idioma:	inglés
OAI Identifier:	oai:repositorio.unican.es:10902/39140
Acceso en línea:	https://hdl.handle.net/10902/39140
Access Level:	acceso abierto
Palabra clave:	Trihalomethanes Colorectal cancer Gene-environment interaction Drinking water

id	ES_0deceb1dbf1bdf1f1d19bb3b19fb2b32
oai_identifier_str	oai:repositorio.unican.es:10902/39140
network_acronym_str	ES
network_name_str	España
repository_id_str
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, Ferrán Trihalomethanes Colorectal cancer Gene-environment interaction Drinking water
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, Ferrán Obón-Santacana, Mireia Rius-Sansalvador, Blanca Guinó, Elisabet Moragas, Núria Donat-Vargas, Carolina Fernández de Larrea-Baz, Nerea Molina-Barceló, Ana Guevara, Marcela Morón-Durán, Francisco D. Dierssen Sotos, Trinidad Tardón, Adonina Castaño-Vinyals, Gemma Cabrera-Castro, Natalia Molina, Antonio José Aizpurua, Amaia Morales-Suárez-Varela, María M. Martín, Vicente Fernández-Navarro, Pablo Villanueva, Cristina M.
author	Moratalla-Navarro, Ferrán
author_facet	Moratalla-Navarro, Ferrán Obón-Santacana, Mireia Rius-Sansalvador, Blanca Guinó, Elisabet Moragas, Núria Donat-Vargas, Carolina Fernández de Larrea-Baz, Nerea Molina-Barceló, Ana Guevara, Marcela Morón-Durán, Francisco D. Dierssen Sotos, Trinidad Tardón, Adonina Castaño-Vinyals, Gemma Cabrera-Castro, Natalia Molina, Antonio José Aizpurua, Amaia Morales-Suárez-Varela, María M. Martín, Vicente Fernández-Navarro, Pablo Villanueva, Cristina M.
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-Durán, Francisco D. Dierssen Sotos, Trinidad Tardón, Adonina Castaño-Vinyals, Gemma Cabrera-Castro, Natalia Molina, Antonio José Aizpurua, Amaia Morales-Suárez-Varela, María M. Martín, Vicente Fernández-Navarro, Pablo Villanueva, Cristina M.
author2_role	author author author author author author author author author author author author author author author author author author author
dc.contributor.none.fl_str_mv	Universidad de Cantabria
dc.subject.none.fl_str_mv	Trihalomethanes Colorectal cancer Gene-environment interaction Drinking water
topic	Trihalomethanes Colorectal cancer Gene-environment interaction Drinking water
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 2026-01-01
dc.type.none.fl_str_mv	journal article http://purl.org/coar/resource_type/c_6501 NA http://purl.org/coar/version/c_be7fb7dd8ff6fe43
dc.type.openaire.fl_str_mv	info:eu-repo/semantics/article
format	article
dc.identifier.none.fl_str_mv	https://hdl.handle.net/10902/39140
url	https://hdl.handle.net/10902/39140
dc.language.none.fl_str_mv	Inglés eng
language_invalid_str_mv	Inglés
language	eng
dc.rights.none.fl_str_mv	open access http://purl.org/coar/access_right/c_abf2 Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv	info:eu-repo/semantics/openAccess
rights_invalid_str_mv	open access http://purl.org/coar/access_right/c_abf2 Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv	openAccess
dc.publisher.none.fl_str_mv	Elsevier
publisher.none.fl_str_mv	Elsevier
dc.source.none.fl_str_mv	Environment International, 2026, 207, 110059 reponame:UCrea Repositorio Abierto de la Universidad de Cantabria instname:Universidad de Cantabria (UC)
instname_str	Universidad de Cantabria (UC)
reponame_str	UCrea Repositorio Abierto de la Universidad de Cantabria
collection	UCrea Repositorio Abierto de la Universidad de Cantabria
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_	1869403367152812032
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, FerránObón-Santacana, MireiaRius-Sansalvador, BlancaGuinó, ElisabetMoragas, NúriaDonat-Vargas, CarolinaFernández de Larrea-Baz, NereaMolina-Barceló, AnaGuevara, MarcelaMorón-Durán, Francisco D.Dierssen Sotos, TrinidadTardón, AdoninaCastaño-Vinyals, GemmaCabrera-Castro, NataliaMolina, Antonio JoséAizpurua, AmaiaMorales-Suárez-Varela, María M.Martín, VicenteFernández-Navarro, PabloVillanueva, Cristina M.TrihalomethanesColorectal cancerGene-environment interactionDrinking waterWe 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.This work was partially supported by Programa FORTALECE del Ministerio de Ciencia e Innovación”, through the project number FORT23/00032; Spanish Association Against Cancer (AECC) Scientific Foundation grant GCTRA18022MORE; Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP) action Gen risk; DISCERN HORIZON-MISS-2021-CANCER-02–03 101096888; Instituto de Salud Carlos III–FEDER [PI08/1770, PI08/0533, PI08/1359, PI09/00773-Cantabria, PI09/01286-León, PI09/01903-Valencia, PI09/ 02078-Huelva, PI09/01662-Granada, PI11/01403, PI11/01889-FEDER, PI11/00226, PI11/01810, PI11/02213, PI12/00488, PI12/00265, PI12/01270, PI12/00715, PI12/00150, PI14/01219, PI14/0613, PI15/ 00069, PI15/00914, PI15/01032, PI17CIII/00034]; CIBERESP [CB06/ 02/0073]; Fundación Marqués de Valdecilla [API 10/09]; the Junta de Castilla y León [LE22A10-2]; Conselleria de Sanitat of the Generalitat Valenciana [AP_061/10]; Recercaixa [2010ACUP 00310]; Regional ernment of the Basque Country; Consejería de Sanidad of the Región de Murcia; the European Commission [FOOD-CT-2006–036224-HIWATE]; Fundación Caja de Ahorros de Asturias; and the University of Oviedo; BR-S received a pre-doctoral grant from Instituto de Salud Carlos III -grant PFIS FI21/00056 (co-founded by the European Union). Sample collection of this work was supported by the Plataforma Biobancos (PT17/0015/0024) and ICOBIOBANC, sponsored by the Catalan Institute of Oncology. We thank CERCA Programme, Generalitat de Catalunya for institutional support.ElsevierUniversidad de Cantabria20262026-01-01journal articlehttp://purl.org/coar/resource_type/c_6501NAhttp://purl.org/coar/version/c_be7fb7dd8ff6fe43info:eu-repo/semantics/articlehttps://hdl.handle.net/10902/39140Environment International, 2026, 207, 110059reponame:UCrea Repositorio Abierto de la Universidad de Cantabriainstname:Universidad de Cantabria (UC)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repositorio.unican.es:10902/391402026-06-02T12:39:31Z
score	15,81155

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)

Similares en LA Referencia