Budhwar Sneha, Bahl Charu, Sharma Siddharth, Singh Navneet, Behera Digambar
Department of Biotechnology, Thapar University, Patiala, Punjab-147002, India.
Department of Pulmonary Medicine, Post Graduate Institute of Medical Education and Research (PGIMER), Sector 14, Chandigarh, India.
Curr Genomics. 2018 May;19(4):313-326. doi: 10.2174/1389202918666170915160606.
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.
To study the role of AhR variants (rs2282885, rs10250822, rs7811989, rs2066853) in affect-ing lung cancer susceptibility.
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.
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).
AhR polymorphic variations can significantly contribute towards lung cancer predisposi-tion.
芳烃受体（AhR）是一种广泛表达的配体激活转录因子，当它与外来配体相遇时，会激活编码生物转化酶（如CYP1A1）的基因的转录机制，从而介导多环芳烃和亚硝胺的代谢，而多环芳烃和亚硝胺是香烟烟雾中最常见的致癌物。AhR的多态性变体起着重要作用，被认为是导致个体患肺癌几率增加的原因。
研究AhR变体（rs2282885、rs10250822、rs7811989、rs2066853）在影响肺癌易感性方面的作用。
采用聚合酶链反应-限制性片段长度多态性（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。为了分析高阶相互作用，使用了多因素降维法和分类回归树法。
携带AhR rs7811989变体基因型的受试者显示出两倍的风险（p=0.007），对于携带rs102550822易感等位基因单拷贝或双拷贝的个体也观察到边缘风险（p=0.02）。而rs2066853的变体等位基因显示出强烈的保护作用（p=0.003）。rs2066853突变基因型的肺鳞状细胞癌（SQCC）个体对肺癌也表现出保护作用（比值比=0.30，p=0.0013）。与非吸烟者相比，rs7811989突变基因型和rs10250822突变基因型之间的关联在吸烟者中尤为明显。AhR rs2066853在具有突变基因型的吸烟者中显示出风险降低（p=0.002）。多因素降维法给出了AhR rs2066853与吸烟的最佳相互作用模型（交叉验证一致性=10/10，预测误差=0.42）。
AhR基因多态性变异可显著影响肺癌易感性。
