Arsenic methylation and lung and bladder cancer in a case-control study in northern Chile.
Arsenic methylation and lung and bladder cancer in a case-control study in northern Chile.
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DOI：
10.1016/j.taap.2013.11.014
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发表时间：
2014-01-15
影响因子：
3.8
通讯作者：
Steinmaus C
中科院分区：
文献类型：
--
作者：
Melak D;Ferreccio C;Kalman D;Parra R;Acevedo J;Pérez L;Cortés S;Smith AH;Yuan Y;Liaw J;Steinmaus C
在人体内，摄入的无机砷代谢为甲基砷（MMA），然后代谢为二甲基砷（DMA），尽管这一过程在大多数人中并不完全。MMA的三价形式在体外具有高毒性，以前的研究已经确定了尿砷的比例（%MMA）与几种砷相关疾病之间的关联。然而，迄今为止，人们对砷在肺癌中的作用知之甚少，肺癌是砷相关死亡的最常见原因，也不知道砷对饮用砷浓度较低的水的人的影响（例如，<200 μg/L）。在这项研究中，尿砷代谢产物测定94例肺癌和117例膀胱癌病例和347例人口为基础的控制在北方智利地区的饮用水砷浓度范围很广。通过增加MMA的三分位数，调整年龄、性别和吸烟的肺癌优势比分别为1.00、1.91（95%置信区间（CI），0.99-3.67）和3.26（1.76-6.04）（p趋势<0.001）。膀胱癌的相应比值比分别为1.00、1.81（1.06-3.11）和2.02（1.15-3.54）（p趋势<0.001）。在仅限于砷水浓度<200 μg/L（中位数=60 μg/L）的受试者的分析中，MMA百分比上三分位数的受试者与MMA百分比下三分位数的受试者相比，肺癌和膀胱癌的比值比分别为2.48（1.08-5.68）和2.37（1.01-5.57）。总体而言，这些研究结果提供了证据表明，砷代谢的个体间差异可能是砷相关肺癌的一个重要危险因素，并可能在暴露于相对低砷水浓度的人群中的癌症风险中发挥作用。
In humans, ingested inorganic arsenic is metabolized to monomethylarsenic (MMA) then to dimethylarsenic (DMA), although this process is not complete in most people. The trivalent form of MMA is highly toxic in vitro and previous studies have identified associations between the proportion of urinary arsenic as MMA (%MMA) and several arsenic-related diseases. To date, however, relatively little is known about its role in lung cancer, the most common cause of arsenic-related death, or about its impacts on people drinking water with lower arsenic concentrations (e.g., <200 μg/L). In this study, urinary arsenic metabolites were measured in 94 lung and 117 bladder cancer cases and 347 population-based controls from areas in northern Chile with a wide range of drinking water arsenic concentrations. Lung cancer odds ratios adjusted for age, sex, and smoking by increasing tertiles of %MMA were 1.00, 1.91 (95% confidence interval (CI), 0.99–3.67), and 3.26 (1.76–6.04) (p-trend <0.001). Corresponding odds ratios for bladder cancer were 1.00, 1.81 (1.06–3.11), and 2.02 (1.15–3.54) (p-trend <0.001). In analyses confined to subjects only with arsenic water concentrations <200 μg/L (median=60 μg/L), lung and bladder cancer odds ratios for subjects in the upper tertile of %MMA compared to subjects in the lower two tertiles were 2.48 (1.08–5.68) and 2.37 (1.01–5.57), respectively. Overall, these findings provide evidence that inter-individual differences in arsenic metabolism may be an important risk factor for arsenic-related lung cancer, and may play a role in cancer risks among people exposed to relatively low arsenic water concentrations.
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影响因子：
10.3
作者：
Marshall, Guillermo;Ferreccio, Catterina;Smith, Allan H.
通讯作者：
Smith, Allan H.
影响因子：
5.4
作者：
Lubin, Jay H.;Caporaso, Neil;Alavanja, Michael C. R.
通讯作者：
Alavanja, Michael C. R.
影响因子：
10.4
作者：
Gibb H;Haver C;Gaylor D;Ramasamy S;Lee JS;Lobdell D;Wade T;Chen C;White P;Sams R
通讯作者：
Sams R
影响因子：
10.4
作者：
Chung JS;Kalman DA;Moore LE;Kosnett MJ;Arroyo AP;Beeris M;Mazumder DN;Hernandez AL;Smith AH
通讯作者：
Smith AH
影响因子：
3.3
作者：
MARAFANTE, E;RADE, J;FOA, V
通讯作者：
FOA, V