Whole exome sequencing reveals DNA repair gene variants in women exposed to chronic arsenic poisoning

Chronic arsenic exposure represents a major public health concern in regions with contaminated groundwater, where long-term bioaccumulation may lead to adverse health outcomes. This study explores the potential genotoxic effects of arsenic exposure in women residing in an arsenic-endemic region by integrating multi-matrix arsenic quantification with whole exome sequencing (WES). Arsenic concentrations were measured in blood, urine, and breast milk samples from nine participants. Elevated arsenic levels were detected across all biological matrices, with each participant exceeding WHO or CDC recommended limits in at least one sample type. Notably, eight of the nine women exhibited breast milk arsenic concentrations above the 1 µg/L reference level, indicating a potential exposure pathway for infants during lactation. Whole exome sequencing identified rare or novel variants in key DNA repair genes in two participants, including a likely pathogenic ATM missense variant (c.590G > A; p.Gly197Glu) and a novel MSH6 variant (c.3716 T > C; p.Ile1239Thr) predicted to be damaging by computational analyses. These genes play essential roles in DNA damage response and mismatch repair pathways that are important for maintaining genomic stability. Although the small sample size (n = 9) limits causal interpretation, these findings provide preliminary evidence suggesting a possible association between chronic arsenic exposure and alterations in DNA repair genes. The study highlights the value of integrating environmental exposure assessment with genomic analysis and provides a hypothesis-generating foundation for future large-scale investigations into gene–environment interactions in arsenic-exposed populations.