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. T he 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.
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