Office of Environmental Health Hazard Assessment, California Environmental Protection Agency, Oakland, CA, USA.
Toxicol Appl Pharmacol. 2010 Sep 1;247(2):138-45. doi: 10.1016/j.taap.2010.06.006. Epub 2010 Jun 17.
In humans, ingested inorganic arsenic is metabolized to monomethylarsenic (MMA) then to dimethylarsenic (DMA), although in most people this process is not complete. Previous studies have identified associations between the proportion of urinary MMA (%MMA) and increased risks of several arsenic-related diseases, although none of these reported on lung cancer. In this study, urinary arsenic metabolites were assessed in 45 lung cancer cases and 75 controls from arsenic-exposed areas in Cordoba, Argentina. Folate has also been linked to arsenic-disease susceptibility, thus an exploratory assessment of associations between single nucleotide polymorphisms in folate metabolizing genes, arsenic methylation, and lung cancer was also conducted. In analyses limited to subjects with metabolite concentrations above detection limits, the mean %MMA was higher in cases than in controls (17.5% versus 14.3%, p=0.01). The lung cancer odds ratio for subjects with %MMA in the upper tertile compared to those in the lowest tertile was 3.09 (95% CI, 1.08-8.81). Although the study size was too small for a definitive conclusion, there was an indication that lung cancer risks might be highest in those with a high %MMA who also carried cystathionine beta-synthase (CBS) rs234709 and rs4920037 variant alleles. This study is the first to report an association between individual differences in arsenic metabolism and lung cancer, a leading cause of arsenic-related mortality. These results add to the increasing body of evidence that variation in arsenic metabolism plays an important role in arsenic-disease susceptibility.
在人类中，摄入的无机砷会代谢为一甲基砷（MMA），然后再代谢为二甲基砷（DMA），尽管在大多数人中，这一过程并不完全。先前的研究已经确定了尿中 MMA 的比例（%MMA）与几种与砷相关疾病的风险增加之间存在关联，尽管这些研究均未报告肺癌。在这项研究中，评估了来自阿根廷科尔多瓦砷暴露地区的 45 例肺癌病例和 75 例对照者的尿砷代谢产物。叶酸也与砷病易感性有关，因此还对叶酸代谢基因中单核苷酸多态性与砷甲基化和肺癌之间的关联进行了探索性评估。在仅限于代谢产物浓度高于检测限的受试者的分析中，病例组的平均%MMA 高于对照组（17.5%比 14.3%，p=0.01）。与 MMA 百分位数最低的 tertile 相比，MMA 百分位数最高的 tertile 的肺癌比值比为 3.09（95%CI，1.08-8.81）。尽管该研究的规模太小，无法得出明确的结论，但有迹象表明，%MMA 较高且同时携带胱硫醚-β-合酶（CBS）rs234709 和 rs4920037 变异等位基因的受试者的肺癌风险可能最高。这项研究首次报告了砷代谢个体差异与肺癌之间的关联，肺癌是砷相关性死亡的主要原因。这些结果增加了越来越多的证据，即砷代谢的个体差异在砷病易感性中起着重要作用。
