Veiskarami Parisa, Houshmand Massoud, Seifi Sharareh, Ansarinejad Nafiseh, Fardad Farshid, Abbasi Bahareh
Department of Medical Genetics, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran.
Research Center, Knowledge University, Erbil, Kurdistan Region, Iraq.
Heliyon. 2021 Aug 24;7(9):e07867. doi: 10.1016/j.heliyon.2021.e07867. eCollection 2021 Sep.
Lung cancer is still the leading cause of cancer mortality in all over the world. Nicotine and its derivatives are the most well-known carcinogens that participate in both etiology and progression of lung cancer. The objective of the current study was to investigate whether single nucleotide polymorphisms (SNPs) rs1051730C > T in CHRNA3 and rs3842A > G in ABCB1, two genes contributing in the mechanism of disposition and metabolism of nicotine and its derivatives, could modify the risk of developing lung cancer, as well as nicotine dependence in Iranian.
The genotyping analysis for these two SNPs was conducted in a case-control study of 108 lung cancer cases and 120 healthy controls using ARMS-PCR and Tetra-primer ARMS-PCR techniques. The correlation between studied SNPs and lung cancer was assessed by the regression analysis.
We observed a significant association between lung cancer and rs1051730C > T by using four genetic models: allele (OR:1.83; 95% CI:1.24-2.6; p = 0.002), dominant (OR: 2.19; 95% CI:1.27-3.78; p = 0.005), recessive (OR: 2.25; 95% CI: 1.02-4.95; p = 0.043) and additive (TT vs CC: OR:3.25; 95% CI:1.38-7.60; p = 0.007, CT vs CC: OR:1.96; 95% CI:1.10-3.48; p = 0.021). Furthermore, a significant association between this variant and nicotine dependence (OR: 2.27; 95% CI: 1.52-3.39; p = 0.00005) was reported. However, no association was found for rs3842A > G.
The results suggested that the CHRNA3 rs1051730C > T via a smoking-dependent manner could modify susceptibility to lung cancer among Iranian population.
肺癌仍是全球癌症死亡的主要原因。尼古丁及其衍生物是参与肺癌病因和进展的最著名致癌物。本研究的目的是调查参与尼古丁及其衍生物处置和代谢机制的两个基因——CHRNA3中的单核苷酸多态性(SNP)rs1051730C>T和ABCB1中的rs3842A>G是否会改变伊朗人患肺癌的风险以及尼古丁依赖性。
在一项包含108例肺癌病例和120例健康对照的病例对照研究中,使用扩增阻滞突变系统聚合酶链反应(ARMS-PCR)和四引物ARMS-PCR技术对这两个SNP进行基因分型分析。通过回归分析评估所研究的SNP与肺癌之间的相关性。
通过四种遗传模型,我们观察到肺癌与rs1051730C>T之间存在显著关联:等位基因(比值比:1.83;95%置信区间:1.24-2.6;p=0.002)、显性(比值比:2.19;95%置信区间:1.27-3.78;p=0.005)、隐性(比值比:2.25;95%置信区间:1.02-4.95;p=0.043)和加性(TT与CC相比:比值比:3.25;95%置信区间:1.38-7.60;p=0.007,CT与CC相比:比值比:1.96;95%置信区间:1.10-3.48;p=0.021)。此外,还报告了该变异与尼古丁依赖性之间存在显著关联(比值比:2.27;95%置信区间:1.52-3.39;p=0.00005)。然而,未发现rs3842A>G存在关联。
结果表明,CHRNA3 rs1051730C>T可能通过吸烟依赖的方式改变伊朗人群对肺癌的易感性。