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)
Year: 2026
Type: article
Study design: Observational Study
Abstract: 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 (CHCl 3 ), 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 CHCl 3 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.
Source: Environment International
Authors: Ferran Moratalla-Navarro, Mireia Obón-Santacana, Blanca Rius-Sansalvador, Elisabet Guinó, Núria Moragas, Carolina Donat-Vargas, Nerea Fernández de Larrea-Baz, Ana Molina-Barceló, Marcela Guevara, Francisco D. Morón-Duran, Trinidad Dierssen-Sotos, Adonina Tardón, Gemma Castaño-Vinyals, Natalia Cabrera-Castro, Antonio José Molina, Amaia Aizpurua, María M. Morales-Suárez-Varela, Vicente Martín, Pablo Fernández-Navarro, Cristina M. Villanueva, Victor Moreno
Institutions: Institut d'Investigació Biomédica de Bellvitge, Institut Català d'Oncologia, Universitat de Barcelona, Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública, Karolinska Institutet, Instituto de Salud Carlos III, Centro Nacional de Epidemiología, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana, Instituto de Salud Pública de Navarra, Navarre Institute of Health Research, Universidad de Cantabria, Marqués de Valdecilla University Hospital, Instituto de Investigación Marqués de Valdecilla, Universidad Nebrija, Universitat Pompeu Fabra, Barcelona Institute for Global Health, Instituto Murciano de Investigación Biosanitaria, Universidad de León, Basque Government, Biogipuzkoa Health Research Institute, Universitat de València
Language: English
Subfield: Health, Toxicology and Mutagenesis
Field: Environmental Science
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $4,750
Funders: Fundación Bancaria Caja de Ahorros de Asturias, Centres de Recerca de Catalunya, European Commission, Fundación Científica Asociación Española Contra el Cáncer, Generalitat de Catalunya, Federación Española de Enfermedades Raras, Ministerio de Economía y Competitividad, Generalitat Valenciana, Ministerio de Ciencia e Innovación, Universidad de Oviedo, Junta de Castilla y León, Fundación Marqués de Valdecilla, Associació Catalana d'Universitats Públiques, HORIZON EUROPE Framework Programme, Instituto de Salud Carlos III
Awards: G1343860231, G1418927621, G1563087297, G178315305, G1900157527, G1920609470, G25115478, G2620658983, G2702798117, G2739777946, G3360488230, G3419946538, Discovering the causes of three poorly understood cancers in Europe, G3537113396, G3559709381, Smart Health Community (SHC), promoviendo la medicina basada en el valor., G3635063837, G3771020718, G3807906117, G4171642061, G4251496718, Identificación de marcadores de susceptibilidad genética útiles para el diseño de estrategias personalizadas de cribado, G4502495630, G4561499809, G4628349315, G4706309318, G4764183276, G5394670091, G5432386086, G5578384164, G5724842450, G5942132429, G6260981759, G6302472787, G6425491107, Supervivencia de cáncer colorrectal en el proyecto MCC-Spain: Modelos de predicción que integran datos genéticos y clínico-epidemiológicos, G6737142931, G6771536215, G677632107, G7170192814, G7245015376, G7684029322, G7965376264, Integración de big data genéticos y datos clínicos: supervivencia con cáncer de mama en el estudio MCC-Spain, G8111550955, Integración de big data genéticos y datos clínicos: supervivencia y calidad de vida en participantes con cáncer de próstata en el estudio MCC-Spain, Las uñas de los pies como biomarcador de exposición:significado y relación con la incidencia de cáncer, G8453080119, G8474960557, G8630196938, G8671373477, G8759146715, G8931017233, Perfil molecular del envejecimiento en la patogénesis y pronóstico de la leucemia linfática crónica
OpenAlex ID: W7121392571