Racial differences in the association between SNPs on 15q25.1, smoking behavior, and risk of non-small cell lung cancer.
Racial differences in the association between SNPs on 15q25.1, smoking behavior, and risk of non-small cell lung cancer.
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DOI：
10.1097/jto.0b013e3181b244ef
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发表时间：
2009-10
期刊：
影响因子：
--
通讯作者：
Amos CI
中科院分区：
文献类型：
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作者：
Schwartz AG;Cote ML;Wenzlaff AS;Land S;Amos CI
三项全基因组关联研究发现，染色体15q25.1上的一个区域与肺癌和尼古丁成瘾有关。该区域包括烟碱乙酰胆碱受体亚基基因CHRNA3和CHRNA5。这些研究是在欧洲或欧洲裔美国人中进行的，并没有提供非裔美国人的风险估计。本研究的目的是确定最近发现的15q25.1染色体上的3个snp （rs1051730, rs931794, rs8034191）的遗传变异是否与非裔美国人肺癌的风险有关。数据来源于三个病例对照研究。参与者包括从底特律地区SEER登记处选择的1058例基于人群的非小细胞肺癌病例和1314例在研究中按年龄、种族和性别匹配的对照组。39%的参与者是非裔美国人。在每日吸烟的非裔美国人中，rs1051730（优势比1.59；95%可信区间1.16-2.19）和rs931794（优势比1.39；95%可信区间1.09-1.78）的相关风险增加。在白人病例中，吸烟的数量因基因型的不同而不同，当吸烟量包括在模型中时，风险与三种snp中的任何一种都没有显着相关。这些发现表明，CHRNA3和CHRNA5区域的snp与肺癌风险有关，虽然变异等位基因在非裔美国人中较少出现，但该群体的风险可能高于白人，并且不太可能通过尼古丁依赖反映对肺癌风险的间接影响。
Three genome-wide association studies identified a region on chromosome 15q25.1 associated with lung cancer and measures of nicotine addiction. This region includes nicotinic acetylcholine receptor subunit genes CHRNA3 and CHRNA5. These studies were conducted in European or European American populations and do not provide risk estimates for African Americans. The goal of this study was to determine whether recently identified genetic variation in 3 SNPs (rs1051730, rs931794, rs8034191) on chromosome 15q25.1 contributes to risk of lung cancer in African Americans. Data were derived from three case-control studies. Participants included 1058 population-based non-small cell lung cancer cases selected from the Detroit area SEER registry and 1314 controls matched within study by age, race, and sex. Thirty-nine percent of participants were African American. Risk associated with rs1051730 (odds ratio 1.59; 95% confidence interval 1.16–2.19) and rs931794 (odds ratio 1.39; 95% confidence interval 1.09–1.78) increased in ever smoking African Americans adjusting for cigarettes smoked per day. Among white cases, the number of cigarettes smoked varied by genotype at all three SNPs, and when smoking quantity was included in the models, risk was not significantly associated with any of the three SNPs. These findings suggest that SNPs in the CHRNA3 and CHRNA5 region contribute to lung cancer risk, and while variant alleles are less frequent in African Americans, risk in this group may be greater than in whites and less likely to reflect an indirect effect on lung cancer risk through nicotine dependence.