Precancerous and non-cancer disease endpoints of chronic arsenic exposure: the level of chromosomal damage and XRCC3 T241M polymorphism.
Precancerous and non-cancer disease endpoints of chronic arsenic exposure: the level of chromosomal damage and XRCC3 T241M polymorphism.
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DOI：
10.1016/j.mrfmmm.2010.10.004
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发表时间：
2011-01-10
影响因子：
2.3
通讯作者：
Giri, Ashok K.
中科院分区：
文献类型：
--
作者：
Kundu, Manjari;Ghosh, Pritha;Mitra, Sanhita;Das, J. K.;Sau, T. J.;Banerjee, Saptarshi;States, J. Christopher;Giri, Ashok K.
关键词：
遗传变异在砷敏感性中起重要作用。我们以前的研究表明DNA修复能力不足是砷中毒的易感因素。同源重组修复途径基因XRCC 3的T241 M多态性与多种癌症的相关性被广泛研究。我们研究了XRCC 3 T241 M多态性与砷诱导的癌前病变和非癌疾病结局的相关性。本研究评估了T241 M多态性与砷诱导的皮肤病变、周围神经病变（神经退行性改变）、结膜炎和其他眼部疾病的关联。在印度的西孟加拉进行了一项病例对照研究，涉及206例砷诱导的皮肤病变和215例对照，这些病例没有砷诱导的皮肤病变，具有相似的砷暴露。采用常规PCR-测序方法检测XRCC 3 T241 M多态性。并对染色体畸变试验、砷中毒性神经病和眼病进行了评价。数据显示，至少一个Met等位基因（Met/Met或Thr/Met）的存在对砷诱导的皮肤病变[OR= 0.45，95%CI：0.30 - 0.67]、周围神经病变[OR=0.49，95%CI：0.30-0.82]和结膜炎[OR=0.60，95%CI：0.40-0.92]的发生具有保护作用。还观察到保护性基因型与染色体畸变频率降低之间存在显著相关性。提示Met等位基因对砷致皮肤损害、染色体不稳定、周围神经病变和结膜炎具有保护作用。
Genetic variants are expected to play an important role in arsenic susceptibility. Our previous study revealed deficient DNA repair capacity to be a susceptibility factor for arsenicism. T241M polymorphism in XRCC3 (a homologous recombination repair pathway gene) is widely studied for its association with several cancers. We have investigated the association of XRCC3 T241M polymorphism with arsenic-induced precancerous and non-cancer disease outcomes. The present study evaluated the association of T241M polymorphism with arsenic-induced skin lesions, peripheral neuropathy (neurodegenerative changes), conjunctivitis and other ocular diseases. A case-control study was conducted in West Bengal, India, involving 206 cases with arsenic-induced skin lesions and 215 controls without arsenic-induced skin lesions having similar arsenic exposure. XRCC3 T241M polymorphism was determined using conventional PCR-sequencing method. Chromosomal aberration assay, arsenic-induced neuropathy and ocular diseases were also evaluated. The data revealed that presence of at least one Met allele (Met/Met or Thr/Met) was protective towards development of arsenic-induced skin lesions [OR= 0.45, 95% CI: 0.30 – 0.67], peripheral neuropathy [OR=0.49; 95%CI: 0.30–0.82] and conjunctivitis [OR=0.60; 95%CI: 0.40–0.92]. A significant correlation was also observed between protective genotype and decreased frequency of chromosomal aberrations. Thus the results indicate the protective role of Met allele against the arsenic-induced skin lesions, chromosomal instability, peripheral neuropathy and conjunctivitis.
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