Abstract 4299: Short telomeres are associated with increased risk for arsenic-related skin lesions in Bangladesh

Abstract

Abstract Chronic exposure to arsenic, a human carcinogen, has been shown in epidemiologic studies to increase the risk of arsenical skin lesions (keratosis and melanosis) as well as cancer (including non-melanoma skin cancer). Recent studies suggest that the mechanism of arsenic's toxicity may be related to telomere dysfunction, including altered telomere length (TL), and differential expression of genes involved in telomere maintenance. However, prior studies of arsenic exposure, TL, and skin lesion tend to be small and cross-sectional in nature. In this study, we investigated the association between arsenic exposure and TL (measured by qPCR as T/S ratio), as well as TL and subsequent risk of skin lesion in individuals who are exposed to naturally contaminated drinking water with a wide range of arsenic levels in the Health Effects of Arsenic Longitudinal Study (HEALS) in Araihazar, Bangladesh (2000-2009). In all laboratory analyses, we attempted to randomize samples across plate positions, and in statistical analyses, we controlled for any residual confounding by plate or plate position. All TL data generated showed a strong inverse association with age. In a random sample of the baseline cohort (n = 649), we observed a positive association between water arsenic levels and TL (Ptrend = 0.035), with beta estimates of 0.001, 0.023, and 0.025 for water arsenic levels of 10.1-50ug/L, 50.1-150ug/L and 150+ug/L, respectively, compared to <10ug/L. However the association was not replicated in an independent random sample (n = 1181, Ptrend = 0.176) with beta estimates of 0.007, -0.004, and -0.017. In a nested case-control study comparing skin lesion incident cases diagnosed across a nine year period with sex- and age-matched controls (448 cases and 462 controls), we observed higher incident skin lesion risk with shorter TL (Ptrend = 4.6E-5), with odds ratios of 3.05, 1.30, and 1.21 for the first (shortest), second, and third TL quartiles compared to the longest. Our findings show that arsenic exposure is not strongly associated with TL, indicating that TL is likely not the main mode of action for arsenic's carcinogenic toxicity. However, TL is inversely associated with skin lesion risk, suggesting that short TL may be a biomarker of susceptibility for arsenical skin lesions independent of arsenic exposure. Citation Format: Chenan Zhang, Muhammad Kibriya, Farzana Jasmine, Shantanu Roy, Habibul Ahsan, Brandon L. Pierce. Short telomeres are associated with increased risk for arsenic-related skin lesions in Bangladesh. [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 4299.