Bahl Charu, Sharma Siddharth, Singh Navneet, Behera Digamber
1 Department of Biotechnology, Thapar University, Patiala, India.
2 Department of Pulmonary Medicine, Post Graduate Institute of Education and Medical Research (PGIMER), Chandigarh, India.
Tumour Biol. 2017 Apr;39(4):1010428317695533. doi: 10.1177/1010428317695533.
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.
Wnt信号通路与人类致癌过程有关。轴抑制蛋白2（Axin2）是一种主要的支架蛋白，是Wnt信号通路的拮抗剂，在多种人类癌症中具有作为肿瘤抑制基因的作用。因此，分析了Axin2基因的七个多态性位点与北印度人肺癌易感性的关系。使用PCR-RFLP技术对总共608名受试者的每个多态性位点进行基因分型，其中包括303例病例和305例对照。使用逻辑回归方法进行进一步的关联分析，以获得调整后的优势比和统计学意义。应用多因素降维法（MDR）和分类回归树（CART）分析来评估单核苷酸多态性（SNP）之间的高阶相互作用。在研究的七个多态性位点中，有三个位点对携带Axin2 148 C>T突变基因型、1365 G>A杂合基因型和1712 + 19 G>T杂合基因型的受试者的肺癌风险显示出强烈的保护作用。另一个重要发现是，在具有变异（TT）基因型的肺鳞状细胞癌（SQCC）患者中，Axin2 148 C>T存在显著关联。Axin2 1712 + 19 G>T在具有杂合（GT）基因型的患者中，对所有组织学亚型的风险均有降低作用。MDR分析预测了一个最佳相互作用模型（Axin2 148、Axin2 2062和Axin2 1712 +19），其具有最大的交叉验证一致性（CVC，10/10）和最小的预测误差（0.38）以及显著的排列p值。CART分析给出了广泛的交互组合，这些组合在调节肺癌易感性方面发挥了主要作用。发现Axin2 148和Axin2 1712 + 19在调节肺癌风险中起主要作用。
