Abstract
BACKGROUND: Arsenic exposure increases the risk of several cancers in humans and contributes to genomic instability. Somatic loss of the Y chromosome (LoY) is a potential biomarker of genomic instability and cancer risk. Smoking is associated with LoY, but few other carcinogens have been investigated. We tested the cross-sectional association between arsenic exposure and LoY in leukocytes among genotyped Bangladeshi men (age 20-70 years) from the Health Effects of Arsenic Longitudinal Study. METHODS: We extracted the median of logR-ratios from probes on the Y chromosome (mLRR-chrY) from genotyping arrays (n = 1364) and estimated the percentage of cells with LoY (% LoY) from mLRR-chrY. We evaluated the association between arsenic exposure (measured in drinking water and urine) and LoY using multivariable linear and logistic regression models. The association between LoY and incident arsenic-induced skin lesions was also examined. RESULTS: Ten percent of genotyped men had LoY in at least 5% of cells and % LoY increased with age. Among men randomly selected for genotyping (n = 778), higher arsenic in drinking water, arsenic consumed and urinary arsenic were associated with increased % LoY (P = 0.006, P = 0.06 and P = 0.13, respectively). LoY was associated with increased risk of incident skin lesions (P = 0.008). CONCLUSION: Arsenic exposure was associated with increased LoY, providing additional evidence that arsenic contributes to genomic instability. LoY was associated with developing skin lesions, a risk factor for cancer, suggesting that LoY may be a biomarker of susceptibility in arsenic-exposed populations. The effect of arsenic on somatic events should be further explored in cancer-prone tissue types.