Centre for Addiction and Mental Health, Department of Psychiatry, Department of Pharmacology and Toxicology, University of Toronto, Medical Sciences Bldg, Rm 4326, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.
J Natl Cancer Inst. 2011 Sep 7;103(17):1342-6. doi: 10.1093/jnci/djr237. Epub 2011 Jul 11.
Genetic variations in the CYP2A6 nicotine metabolic gene and the CHRNA5-CHRNA3-CHRNB4 (CHRNA5-A3-B4) nicotinic gene cluster have been independently associated with lung cancer. With genotype data from ever-smokers of European ancestry (417 lung cancer patients and 443 control subjects), we investigated the relative and combined associations of polymorphisms in these two genes with smoking behavior and lung cancer risk. Kruskal-Wallis tests were used to compare smoking variables among the different genotype groups, and odds ratios (ORs) for cancer risk were estimated using logistic regression analysis. All statistical tests were two-sided. Cigarette consumption (P < .001) and nicotine dependence (P = .036) were the highest in the combined CYP2A6 normal metabolizers and CHRNA5-A3-B4 AA (tag single-nucleotide polymorphism rs1051730 G>A) risk group. The combined risk group also exhibited the greatest lung cancer risk (OR = 2.03; 95% confidence interval [CI] = 1.21 to 3.40), which was even higher among those who smoked 20 or fewer cigarettes per day (OR = 3.03; 95% CI = 1.38 to 6.66). Variation in CYP2A6 and CHRNA5-A3-B4 was independently and additively associated with increased cigarette consumption, nicotine dependence, and lung cancer risk. CYP2A6 and CHRNA5-A3-B4 appear to be more strongly associated with smoking behaviors and lung cancer risk, respectively.
基因变异在 CYP2A6 尼古丁代谢基因和 CHRNA5-CHRNA3-CHRNB4（CHRNA5-A3-B4）烟碱基因簇已被独立与肺癌相关。基因型数据从以往吸烟者的欧洲血统（417 肺癌患者和 443 对照组），我们研究了这两个基因的多态性与吸烟行为和肺癌风险的相对和联合关联。Kruskal-Wallis 检验用于比较不同基因型组的吸烟变量，和癌症风险的比值比（ORs）使用 logistic 回归分析进行估计。所有统计检验均为双侧。吸烟量（P <.001）和尼古丁依赖（P =.036）在 CYP2A6 正常代谢者和 CHRNA5-A3-B4 AA（标记单核苷酸多态性 rs1051730 G>A）风险组最高。联合风险组还表现出最大的肺癌风险（OR = 2.03; 95%置信区间 [CI] = 1.21 至 3.40），在每天吸烟 20 支或更少的人群中更高（OR = 3.03; 95% CI = 1.38 至 6.66）。CYP2A6 和 CHRNA5-A3-B4 的变异与增加的吸烟量、尼古丁依赖和肺癌风险独立且呈相加性相关。CYP2A6 和 CHRNA5-A3-B4 似乎分别与吸烟行为和肺癌风险的相关性更强。
