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)

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.