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首页> 外文期刊>Pharmacogenomics >Influence of polymorphisms in MTHFR 677 C-->T, TYMS 3R-->2R and MTR 2756 A-->G on NSCLC risk and response to platinum-based chemotherapy in advanced NSCLC.
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Influence of polymorphisms in MTHFR 677 C-->T, TYMS 3R-->2R and MTR 2756 A-->G on NSCLC risk and response to platinum-based chemotherapy in advanced NSCLC.

机译：MTHFR 677 C-> T，TYMS 3R-> 2R和MTR 2756 A-> G中的多态性对晚期NSCLC中NSCLC风险和对铂类化疗的反应的影响。

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    Aims: Genetic factors may contribute to individual differences in cancer susceptibility, drug efficacy and toxicity. This study was designed to investigate the effects of the polymorphisms of methylenetetrahydrofolate reductase 677 C-->T (MTHFR 677 C-->T), thymidylate synthase (TYMS 3R-->2R),and methionine synthase 2756 A-->G (MTR 2756 A-->G) on the risk of lung cancer and response to platinum-based chemotherapy in advanced non-small-cell lung cancer (NSCLC). Materials & methods: We conducted a case-control study involving 438 NSCLC cases (including 101 follow-up cases) and 641 healthy controls in North China. Results & conclusion: Using a genetic model analysis, the polymorphism MTHFR 677 C-->T showed a significantly increased risk for NSCLC in women but not in men, which was observed in the codominant model (CT vs CC adjusted odds ratio [OR] = 2.46; 95% confidence interval [CI]: 1.37-4.42; p = 0.003; TT vs CC adjusted OR: 2.04; 95% CI: 1.09-3.81; p = 0.03) and the dominant model (CT + TT vs CC adjusted OR: 2.30; 95% CI: 1.31-4.05; p = 0.004). In addition, we found that patients with the MTHFR 677 TT genotype showed a better response to platinum-based chemotherapy in the recessive model (TT vs CT + CC adjusted OR: 0.24; 95% CI: 0.09-0.68; p = 0.007), the generalized OR was 0.44 (0.22-0.88; p = 0.04). There were no significant associations of the polymorphisms of TYMS 3R-->2R or MTR 2756 A-->G with the risk of NSCLC or response to platinum-based chemotherapy in advanced NSCLC in any genetic model. Our results suggest that genetic polymorphisms of MTHFR 677 C-->T may contribute to NSCLC development in Chinese women and could also influence treatment response for advanced NSCLC patients with platinum-based chemotherapy. Further studies with larger sample sizes are required to validate this association. Original submitted 4 October 2010; Revised submitted 14 February 2011.
    机译：目的：遗传因素可能会导致癌症易感性，药物疗效和毒性方面的个体差异。本研究旨在研究亚甲基四氢叶酸还原酶677 C-> T（MTHFR 677 C-> T），胸苷酸合酶（TYMS 3R-> 2R）和蛋氨酸合酶2756 A-> G多态性的影响。 （MTR 2756 A-> G）对晚期非小细胞肺癌（NSCLC）的肺癌风险和对铂类化学疗法的反应。材料与方法：我们在华北地区进行了438例NSCLC病例（包括101例随访病例）和641例健康对照的病例对照研究。结果与结论：使用遗传模型分析，多态性MTHFR 677 C-> T显示女性罹患NSCLC的风险显着增加，而男性则不然，这在共有模型中观察到（CT与CC校正比值比[OR] = 2.46; 95％置信区间[CI]：1.37-4.42; p = 0.003; TT与CC调整后的OR：2.04; 95％CI：1.09-3.81; p = 0.03）和主导模型（CT + TT与CC调整后） OR：2.30; 95％CI：1.31-4.05; p ＝ 0.004）。此外，我们发现MTHFR 677 TT基因型的患者在隐性模型中显示出对铂类化疗更好的反应（TT vs CT + CC调整后的OR：0.24; 95％CI：0.09-0.68; p = 0.007），广义OR为0.44（0.22-0.88; p = 0.04）。在任何遗传模型中，TYMS 3R-> 2R或MTR 2756 A-> G的多态性与晚期NSCLC的NSCLC风险或对铂类化学疗法的反应均无显着相关性。我们的结果表明，MTHFR 677 C-> T的遗传多态性可能有助于中国女性发展NSCLC，也可能影响铂类化学疗法治疗晚期NSCLC患者的治疗反应。需要进行更大样本量的进一步研究以验证这种关联。原件于2010年10月4日提交;修订于2011年2月14日提交。

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