Background: AhR, a ubiquitously expressed ligand-activated transcription factor, upon its encounter with the foreign ligands activates the transcriptional machinery of genes encoding for bio-transformation enzymes like CYP1A1 hence, mediating the metabolism of Poly aromatic hydrocarbons and nitrosamines which account for the maximally found carcinogen in cigarette smoke. Polymorphic variants of AhR play a significant role and are held responsible for disposing the individuals with greater chances of acquiring lung cancer. Objective: To study the role of AhR variants (rs2282885, rs10250822, rs7811989, rs2066853) in affect-ing lung cancer susceptibility. Methods: 297 cases and 320 controls have been genotyped using PCR-RFLP technique. In order to find out the association, unconditional logistic regression approach was used. To analyze high order in-teractions Multifactor Dimensionality Reduction and Classification and regression tree was used. Results: Subjects carrying the variant genotype for AhR rs7811989 showed a two-fold risk (p=0.007) and a marginal risk was also seen in case of individuals carrying either single or double copy of suscep-tible allele for rs102550822 (p=0.02). Whereas the variant allele for rs2066853 showcased a strong pro-tective effect (p=0.003). SQCC individuals with mutant genotype of rs2066853 also exhibited a protec-tive effect towards lung cancer (OR=0.30, p=0.0013). The association of rs7811989 mutant genotype and rs10250822 mutant genotype was evident especially in smokers as compared to non-smokers. AhR rs2066853 showed a decreased risk in smokers with mutant genotype (p=0.002). MDR approach gave the best interaction model of AhR rs2066853 and smoking (CVC=10/10, prediction error=0.42). Conclusion: AhR polymorphic variations can significantly contribute towards lung cancer predisposi-tion.

中文翻译：

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AhR 基因序列变异对调节北印度人群吸烟诱发肺癌易感性的作用：多重相互作用分析

背景：AhR 是一种普遍表达的配体激活转录因子，在遇到外源配体时，会激活编码生物转化酶（如 CYP1A1）的基因的转录机制，从而介导多芳烃和亚硝胺的代谢，这在很大程度上是在香烟烟雾中发现致癌物。AhR 的多态性变体发挥重要作用，并负责处理个体患肺癌的更大机会。目的：研究AhR变异体（rs2282885、rs10250822、rs7811989、rs2066853）在影响肺癌易感性中的作用。方法：采用PCR-RFLP技术对297例病例和320例对照进行基因分型。为了找出关联，使用了无条件逻辑回归方法。为了分析高阶交互，使用了多因素降维和分类以及回归树。结果：携带 AhR rs7811989 变异基因型的受试者显示出两倍的风险（p=0.007），并且在携带 rs102550822 易感等位基因的单拷贝或双拷贝的个体中也观察到了边际风险（p=0.02） . 而 rs2066853 的变异等位基因表现出很强的保护作用 (p=0.003)。具有 rs2066853 突变基因型的 SQCC 个体也表现出对肺癌的保护作用（OR=0.30，p=0.0013）。与非吸烟者相比，rs7811989 突变基因型和 rs10250822 突变基因型的关联在吸烟者中尤为明显。AhR rs2066853 显示突变基因型吸烟者的风险降低（p=0.002）。MDR 方法给出了 AhR rs2066853 和吸烟的最佳交互模型（CVC=10/10，预测误差=0.42）。结论：AhR多态性变异对肺癌易感性有显着影响。