Polymorphisms in the Caspase Genes and the Risk of Lung Cancer
Polymorphisms in the Caspase Genes and the Risk of Lung Cancer
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DOI：
10.1097/jto.0b013e3181e04543
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发表时间：
2010-08-01
影响因子：
20.4
通讯作者：
Park, Jae Yong
中科院分区：
文献类型：
--
作者：
Lee, Shin Yup;Choi, Yi Young;Park, Jae Yong
简介：半胱天冬酶（CASP）是细胞凋亡途径的重要调节者和执行者，在癌症的发生和发展中发挥着至关重要的作用。基于CASPs在细胞凋亡通路中的相互作用，我们评估了CASP3、6、7、8、9和10基因的11个多态性与肺癌风险之间的关联。方法：对720例肺癌患者和720例年龄和性别频率匹配的健康对照进行基因型测定。结果：在个体多态性分析中，CASP7 rs2227310C>在每个多态性的变异等位基因的隐性和显性模型下，G和CASP9 rs4645981C > T分别与肺癌风险增加1.40倍和1.28倍相关。在 CASP3 77G > A 的情况下，与至少具有一种变异等位基因的受试者相比，具有 GG 基因型的受试者患肺癌的风险增加 1.19 倍。当三种多态性结合时，随着风险基因型数量的增加，肺癌的风险以剂量依赖性方式增加（p（趋势）<0.001）。与零风险基因型的受试者相比，具有两种和三种风险基因型的受试者患肺癌的风险显着增加（调整后的优势比 = 1.56，95% 置信区间 = 1.14-2.13，p = 0.005，调整后的优势比 = 2.54，95% 置信区间 = 1.28 -5.02，p = 0.008）。结论：这些结果表明这三个 CASP 基因多态性的联合分析可能比单一多态性的分析更好地预测肺癌的风险。
Introduction: Caspases (CASPs) are important regulators and executioners in apoptosis pathway and play a crucial role in the development and progression of cancer. On the basis of the interactions of CASPs in the apoptotic pathway, we evaluated the association between 11 polymorphisms of CASP3, 6, 7, 8, 9, and 10 genes and the risk of lung cancer.Methods: The genotypes were determined in 720 patients with lung cancer and 720 healthy controls frequency matched for age and gender.Results: In individual polymorphism analysis, the CASP7 rs2227310C > G and CASP9 rs4645981C > T were associated with 1.40-fold and 1.28-fold increased risk of lung cancer under recessive and dominant models for the variant allele of each polymorphism, respectively. In the case of the CASP3 77G > A, subjects with the GG genotype were at a 1.19-fold increased risk of lung cancer compared with those with at least one variant allele. When the three polymorphisms were combined, the risk of lung cancer increased in a dose-dependent manner as the number of risk genotypes increased (p(trend) < 0.001). Subjects with two and three risk genotypes carried a significantly increased risk of lung cancer compared with those with zero risk genotype (adjusted odds ratio = 1.56, 95% confidence interval = 1.14-2.13, p = 0.005 and adjusted odds ratio = 2.54, 95% confidence interval = 1.28 -5.02, p = 0.008, respectively).Conclusions: These results suggest that a combined analysis of these three CASP gene polymorphisms might better predict the risk of lung cancer than analysis of a single polymorphism.