Association study between genetic variations in Axin2 gene and lung cancer risk in North Indian population: A multiple interaction analysis
Association study between genetic variations in Axin2 gene and lung cancer risk in North Indian population: A multiple interaction analysis
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DOI：
10.1177/1010428317695533
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发表时间：
2017-04-01
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影响因子：
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通讯作者：
Behera, Digamber
中科院分区：
文献类型：
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作者：
Bahl, Charu;Sharma, Siddharth;Behera, Digamber
Wnt通路参与了人类肿瘤的发生发展过程。轴抑制蛋白2（Axin 2）是Wnt信号通路的主要支架蛋白，在多种肿瘤中作为抑癌基因发挥作用。因此，分析了Axin 2基因的7个多态性位点与北印度人肺癌易感性的关系。采用PCR-RFLP技术对608名受试者进行了基因分型，其中303名为病例组，305名为对照组。采用logistic回归方法进行进一步的关联分析，以获得调整后的比值比和统计学显著性。应用MDR和CART分析来评估SNP之间的高阶相互作用。在Axin 2 148 C > T突变基因型和1365 G > A和1712 + 19 G > T杂合基因型的受试者中，7个多态性位点中的3个显示出对肺癌风险的强保护作用。另一个重要的发现是Axin 2 148 C > T在具有变异（TT）基因型的SQCC患者中的显著关联。Axin 21712 + 19 G > T基因型在GT型患者中对所有组织学亚型的风险均降低。MDR分析预测了最佳相互作用模型（Axin 2 148、Axin 2 2062和Axin 2 1712 + 19），具有最大CVC（10/10）和最小预测误差（0.38），沿着具有显著排列p值。CART分析给出了广泛的交互组合，其在调节肺癌易感性中表现出重大贡献。Axin 2 148和Axin 2 1712 + 19在调节肺癌风险中起主要作用。
Wnt pathway has been implicated in the process of human carcinogenesis. Axis inhibition protein2 (Axin2), a major scaffold protein is an antagonist of Wnt pathway and is potent to act as a tumor suppressor gene in various human cancers. Therefore, the seven polymorphic sites of Axin2 gene were analyzed, in relation to lung cancer susceptibility in North Indians. A total of 608 subjects were genotyped using PCR-RFLP technique for each polymorphic site including 303 cases and 305 controls. Further association analysis was carried out using logistic regression approach to obtain adjusted odds ratio and statistical significance. MDR and CART analysis were applied to evaluate high order interactions between the SNP's. Three out of seven studied polymorphic sites showed a strong protective effect in subjects having mutant genotype for Axin2 148 C > T and heterozygous genotype for 1365 G > A and 1712 + 19 G > T towards lung cancer risk. The other important finding was the significant association of Axin2 148 C > T in SQCC patients having variant (TT) genotype. Axin2 1712 + 19 G > T showed a decreased risk for all the histological subtypes in patients with heterozygous (GT) genotype. MDR analysis predicted a best interaction model (Axin2 148, Axin2 2062 and Axin2 1712 + 19) with maximum CVC (10/10) and minimum prediction error (0.38) along with significant permutation p-value. CART analysis gave a wide spectrum of interactive combinations which exhibited a major contribution in modulating lung cancer susceptibility. Axin2 148 and Axin2 1712 + 19 were found to play a major role in modulating lung cancer risk.