Abstract 4303: Arsenic exposure and mosaic loss of the Y chromosome among Bangladeshi men

Background: Exposure to drinking water contaminated with arsenic, a known carcinogen, is a serious global health issue, increasing risk for several types of cancer, as well as overall mortality. Somatic mosaic loss of the Y chromosome (LoY) is the most frequent known somatic chromosomal aberration in men, and LoY in peripheral blood cells has been associated with exposure to cigarette smoke, as well as cancer risk and overall mortality. In this work, we examine the correlates of LoY among 2,588 male members of an arsenic-exposed Bangladeshi cohort (mean age: 42 years). Methods: DNA was extracted from peripheral blood at baseline interview, and genome-wide SNP data was generated using Illumina arrays. We assessed LoY using the median Log R Ratio (mLRR) for 2,882 SNPs located in the male-specific region of chromosome Y. Within each of five different genotyping batches, we classified individuals have having LoY if their mLRR-Y value fell below the 2nd percentile of an mLRR distribution simulated assuming no LoY. Arsenic exposure was measured as the arsenic concentration in participants’ primary drinking wells (reported at baseline). All association estimates were adjusted for age, BMI, and smoking status. Results: We detected LoY for a total of 305 men across 5 different genotyping batches, with rates of LoY ranging from 7% to 18% across batches. Age showed a consistent positive association with LoY across all batches, consistent with prior studies. Among the two genotyping batches representing random samples of the cohort (n = 391 and n = 344), quartiles of increasing arsenic concentration in drinking water were associated with increased LoY (P-trend = 0.05 in both batches). In a comparison of 297 individuals with incident arsenical skin lesions (the most common sign of arsenic toxicity) and 673 control individuals (randomly selected from the cohort), LoY was significantly more common in cases than controls (P = 0.001); however, this association was attenuated after adjusting for arsenic exposure (P = 0.22). In an analysis of all 2,588 individuals (including non-randomly-sampled case groups), current smoking showed a suggestive association with increased LoY (P = 0.06), consistent with a prior studies of older populations. Conclusion: In this population-based study of arsenic-exposed Bangladeshi men of a wide range of ages, increasing exposure to arsenic, a known carcinogen, was associated with increased risk of LoY, and LoY was more common among men with subsequent arsenic toxicity (i.e., arsenical skin lesions). This study provides evidence that a carcinogenic environmental exposure causes the most common form of genetic mutation in men. Additional research is needed to determine if LoY is causally involved in arsenic-induced carcinogenesis or if LoY is simply a marker of exposure. Citation Format: Brandon L. Pierce, Muhammad Kibriya, Farzana Jasmine, Joseph Graziano, Habibul Ahsan. Arsenic exposure and mosaic loss of the Y chromosome among Bangladeshi men. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4303.