Yager Janice W, Erdei Esther, Myers Orrin, Siegel Malcolm, Berwick Marianne
Division of Epidemiology, Biostatistics and Preventive Medicine, Health Sciences Center, Department of Internal Medicine, University of New Mexico, Albuquerque, NM, USA.
ENVIRON International Corporation, 2200 Powell Street, Suite 700, Emeryville, CA, 94608, USA.
Environ Geochem Health. 2016 Jun;38(3):897-910. doi: 10.1007/s10653-015-9770-4. Epub 2015 Oct 7.
Cases of cutaneous melanoma and controls were enrolled in a New Mexico population-based study; subjects were administered questionnaires concerning ultraviolet (UV) and inorganic arsenic (iAs) exposure. Historical iAs exposure was estimated. UV exposure estimates were also derived using geospatial methods. Drinking water samples were collected for iAs analysis. Blood samples were collected for DNA repair (Comet) and DNA repair gene polymorphism assays. Arsenic concentrations were determined in urine and toenail samples. UV exposures during the previous 90 days did not vary significantly between cases and controls. Mean (±SD) current home iAs drinking water was not significantly different for cases and controls [3.98 μg/L (±3.67) vs. 3.47 μg/L (±2.40)]. iAs exposure showed no effect on DNA repair or association with melanoma. Results did not corroborate a previously reported association between toenail As and melanoma risk. Arsenic biomarkers in urine and toenail were highly significantly correlated with iAs in drinking water. A UV-DNA repair interaction for UV exposure over the previous 7-90 days was shown; cases had higher DNA damage than controls at low UV values. This novel finding suggests that melanoma cases may be more sensitive to low-level UV exposure than are controls. A UV-APEX1 interaction was shown. Subjects with the homozygous rare APEX1 DNA repair gene allele had a higher risk of early melanoma diagnosis at low UV exposure compared with those with the homozygous wild type or the heterozygote. Notably, a UV-arsenic interaction on inhibition of DNA repair was not observed at iAs drinking water concentrations below 10 ppb (μg/L).
皮肤黑色素瘤病例和对照者参与了一项基于新墨西哥州人群的研究；研究对象接受了关于紫外线（UV）和无机砷（iAs）暴露的问卷调查。估计了既往iAs暴露情况。还使用地理空间方法得出了UV暴露估计值。采集饮用水样本进行iAs分析。采集血液样本进行DNA修复（彗星试验）和DNA修复基因多态性检测。测定尿液和趾甲样本中的砷浓度。病例组和对照组在前90天的UV暴露无显著差异。病例组和对照组当前家庭饮用水中iAs的平均（±标准差）含量无显著差异[3.98μg/L（±3.67）对3.47μg/L（±2.40）]。iAs暴露对DNA修复无影响，也与黑色素瘤无关联。结果并未证实先前报道的趾甲砷与黑色素瘤风险之间的关联。尿液和趾甲中的砷生物标志物与饮用水中的iAs高度显著相关。研究显示了过去7 - 90天UV暴露的UV - DNA修复相互作用；在低UV值时，病例组的DNA损伤高于对照组。这一新发现表明，黑色素瘤病例可能比对照组对低水平UV暴露更敏感。研究显示了UV - APEX1相互作用。与纯合野生型或杂合子相比，具有纯合罕见APEX1 DNA修复基因等位基因的受试者在低UV暴露下早期黑色素瘤诊断风险更高。值得注意的是，在饮用水iAs浓度低于10 ppb（μg/L）时，未观察到UV - 砷对DNA修复抑制的相互作用。
