Zhou Wenjing, Geng Tingting, Wang Huijuan, Xun Xiaojie, Feng Tian, Zou Hui, Kang Longli, Jin Tianbo, Chen Chao
School of Life Sciences, Northwest University, Xi'an, 710069, Shaanxi, China.
Tumour Biol. 2015 Jul;36(7):4987-92. doi: 10.1007/s13277-015-3149-0. Epub 2015 Feb 6.
Lung cancer is the leading cause of cancer-related deaths worldwide that result from the combined effected of smoking exposure and genetic susceptibility. CHRNA3, a nicotinic acetylcholine receptor gene, was associated with lung cancer risk. The aim of this study was to identify whether CHRNA3 polymorphisms increase lung cancer risk directly or indirectly through smoking behavior in the Chinese Han individuals. We conducted a case-control study including 228 individuals with lung cancer and 301 healthy individuals. Seventeen known SNPs within CHRNA3 were selected for genotyping. Odds ratios (OR) and 95 % confidence interval (CI) were calculated by unconditional logistic regression with adjustment for gender and age. Two SNPs (rs8042059 and rs7177514) showed a 1.54-fold (p = 0.036; 95 % CI = 1.03-2.32) and 1.52-fold (p = 0.043; 95 % CI = 1.01-2.27) increased risk for lung cancer in smokers, respectively. Rs8042059 also showed a significant association for variant genotypes (CA/AA) compared with the wild-type genotype (CC), with an OR = 1.84 (p = 0.042; 95 % CI, 1.02-3.33) in the dominant model. In addition, the haplotype analysis found that the haplotypes "TCAC" and "CTGT," composed of rs938682, rs12914385, rs11637630, and rs2869546, were associated with a 1.79-fold and 501-fold increased lung cancer risk, respectively. However, the polymorphisms of all SNPs were not significantly different between controls and cases among general or nonsmokers population. Rs8042059 and rs7177514 may increase lung cancer risk indirectly through smoking behavior in the Chinese Han population.
肺癌是全球癌症相关死亡的主要原因，这是由吸烟暴露和遗传易感性的综合影响导致的。CHRNA3是一种烟碱型乙酰胆碱受体基因，与肺癌风险相关。本研究的目的是确定CHRNA3基因多态性在中国汉族个体中是直接还是通过吸烟行为间接增加肺癌风险。我们进行了一项病例对照研究，包括228例肺癌患者和301例健康个体。选择CHRNA3内的17个已知单核苷酸多态性（SNP）进行基因分型。通过无条件逻辑回归计算比值比（OR）和95%置信区间（CI），并对性别和年龄进行调整。两个SNP（rs8042059和rs7177514）在吸烟者中分别显示出肺癌风险增加1.54倍（p = 0.036；95%CI = 1.03 - 2.32）和1.52倍（p = 0.043；95%CI = 1.01 - 2.27）。与野生型基因型（CC）相比，rs8042059在显性模型中对于变异基因型（CA/AA）也显示出显著关联，OR = 1.84（p = 0.042；95%CI，1.02 - 3.33）。此外，单倍型分析发现，由rs938682、rs12914385、rs11637630和rs2869546组成的单倍型“TCAC”和“CTGT”分别与肺癌风险增加1.79倍和5.01倍相关。然而，在总体或非吸烟人群的对照组和病例组之间，所有SNP的多态性没有显著差异。rs8042059和rs7177514可能通过中国汉族人群的吸烟行为间接增加肺癌风险。
