Andrew Angeline S, Mason Rebecca A, Kelsey Karl T, Schned Alan R, Marsit Carmen J, Nelson Heather H, Karagas Margaret R
Department of Community & Family Medicine, Section of Biostatistics & Epidemiology, Dartmouth Medical School, Lebanon, NH 03756, United States.
Toxicol Lett. 2009 May 22;187(1):10-4. doi: 10.1016/j.toxlet.2009.01.013. Epub 2009 Jan 20.
Drinking water arsenic exposure has been associated with increased bladder cancer susceptibility. Epidemiologic and experimental data suggest a co-carcinogenic effect of arsenic with exposure to DNA damaging agents, such as cigarette smoke. Recent evidence further supports the hypothesis that genetic variation in DNA repair genes can modify the arsenic-cancer relationship, possibly because arsenic impairs DNA repair capacity. We tested this hypothesis in a population-based study of bladder cancer with XRCC3, ERCC2 genotype/haplotype and arsenic exposure data on 549 controls and 342 cases. Individual exposure to arsenic was determined in toenail samples by neutron activation. Gene-environment interaction with arsenic exposure was observed in relation to bladder cancer risk for a variant allele of the double-strand break repair gene XRCC3 T241M (adjusted OR 2.8 (1.1-7.3)) comparing to homozygous wild type among those in the top arsenic exposure decile (interaction p-value 0.01). Haplotype analysis confirmed the association of the XRCC3 241. Thus, double-strand break repair genotype may enhance arsenic associated bladder cancer susceptibility in the U.S. population.
饮用水中砷暴露与膀胱癌易感性增加有关。流行病学和实验数据表明，砷与接触DNA损伤剂（如香烟烟雾）具有协同致癌作用。最近的证据进一步支持了这样的假说，即DNA修复基因的遗传变异可以改变砷与癌症的关系，这可能是因为砷会损害DNA修复能力。我们在一项基于人群的膀胱癌研究中对这一假说进行了检验，该研究纳入了549名对照和342例病例，有XRCC3、ERCC2基因型/单倍型以及砷暴露数据。通过中子活化法测定趾甲样本中的个体砷暴露量。与双链断裂修复基因XRCC3 T241M的一个变异等位基因相关的砷暴露与膀胱癌风险之间存在基因-环境相互作用（调整后的比值比为2.8（1.1 - 7.3）），在砷暴露最高十分位数人群中，与纯合野生型相比（相互作用p值为0.01）。单倍型分析证实了XRCC3 241的关联。因此，双链断裂修复基因型可能会增强美国人群中砷相关的膀胱癌易感性。
