BACKGROUND Chronic arsenic exposure is associated with increased risk for arsenical skin lesions, cancer, and other adverse health outcomes. One potential mechanism of arsenic toxicity is telomere dysfunction. However, prior epidemiological studies of arsenic exposure, telomere length (TL), and skin lesion are small and cross-sectional. We investigated the associations between arsenic exposure and TL and between baseline TL and incident skin lesion risk among individuals participating in the Health Effects of Arsenic Longitudinal Study in Bangladesh (2000-2009). METHODS Quantitative PCR was used to measure the average TL of peripheral blood DNA collected at baseline. The association between baseline arsenic exposure (well water and urine) and TL was estimated in a randomly-selected subcohort (n = 1469). A nested case-control study (466 cases and 464 age- and sex-matched controls) was used to estimate the association between baseline TL and incident skin lesion risk (diagnosed < 8 years after baseline). RESULTS No association was observed between arsenic exposure (water or urine) and TL. Among incident skin lesion cases and matched controls, we observed higher skin lesion risk among individuals with shorter TL (Ptrend = 1.5 × 10-5) with odds ratios of 2.60, 1.59, and 1.10 for the first (shortest), second, and third TL quartiles compared to the fourth (longest). CONCLUSIONS Arsenic exposure was not associated with TL among Bangladeshi adults, suggesting that leukocyte TL may not reflect a primary mode of action for arsenic's toxicity. However, short TL was associated with increased skin lesion risk, and may be a biomarker of arsenic susceptibility modifying arsenic's effect on skin lesion risk.

中文翻译：

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孟加拉队列中端粒长度、砷暴露和砷毒性的研究。

背景技术慢性砷暴露与砷皮肤损伤、癌症和其他不良健康结果的风险增加有关。砷毒性的一种潜在机制是端粒功能障碍。然而，先前关于砷暴露、端粒长度 (TL) 和皮肤损伤的流行病学研究规模较小且具有横断面性。我们调查了参与孟加拉国砷纵向研究的健康影响（2000-2009 年）的个体中砷暴露与 TL 之间以及基线 TL 与皮肤损伤风险之间的关联。方法 定量 PCR 用于测量在基线收集的外周血 DNA 的平均 TL。在随机选择的亚组（n = 1469）中估计基线砷暴露（井水和尿液）与 TL 之间的关联。使用嵌套病例对照研究（466 例病例和 464 例年龄和性别匹配的对照）来估计基线 TL 与皮肤损伤风险（基线后诊断 < 8 年）之间的关联。结果 未观察到砷暴露（水或尿液）与 TL 之间存在关联。在皮肤损伤病例和匹配对照中，我们观察到 TL 较短 (Ptrend = 1.5 × 10-5) 个体的皮肤损伤风险较高，第一（最短）、第二和第三的优势比分别为 2.60、1.59 和 1.10 TL 四分位数与第四个（最长）相比。结论 孟加拉成年人的砷暴露与 TL 无关，这表明白细胞 TL 可能不能反映砷毒性的主要作用模式。然而，短 TL 与皮肤损伤风险增加有关，