人染色体8p11(CHRNB3-CHRNA6)区域基因多态性与中国汉族人群肺癌易感性的相关性

doi:10.3724/SP.J.1005.2011.00886

遗传 ›› 2011, Vol. 33 ›› Issue (8): 886-894.doi: 10.3724/SP.J.1005.2011.00886

人染色体8p11(CHRNB3-CHRNA6)区域基因多态性与中国汉族人群肺癌易感性的相关性

张晓博¹, 赵振宏¹, 陈红岩¹, 王久存¹, 钱吉¹, 杨亚军¹, 魏庆义², 黄建³, 卢大儒¹

1. 复旦大学生命科学学院遗传工程国家重点实验室, 上海 200433 2. 美国德州大学M.D.Anderson癌症中心流行病学系, 休斯顿 TX 77030-3721 3. 上海交通大学基础医学院生物化学与分子细胞生物学系, 上海 200025

收稿日期:2011-04-14 修回日期:2011-05-11 出版日期:2011-08-20 发布日期:2011-08-25
通讯作者: 卢大儒 E-mail:drlu@fudan.edu.cn
基金资助:
上海市科委重点项目(编号：09JC1402200), 上海市国际合作项目(编号：10410709100)和上海市重点学科建设项目(编号：B111)资助

Human chromosome 8p11 (CHRNB3-CHRNA6) region gene polymorphisms and susceptibility to lung cancer in Chinese Han population

ZHANG Xiao-Bo¹, ZHAO Zhen-Hong¹, CHEN Hong-Yan¹, WANG Jiu-Cun¹, QIAN Ji¹, YANG Ya-Jun¹, WEI Qing-Yi², HUANG Jian³, LU Da-Ru¹

1. State key laboratory of Genetic Engineering, The Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200433, China 2. Department of Epidemiology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, TX 77030-3721, USA 3. Department of Biochemistry and Molecular Cell Biology, Basic Medical College, Shanghai Jiaotong University, Shanghai 200025, China

Received:2011-04-14 Revised:2011-05-11 Online:2011-08-20 Published:2011-08-25
Contact: Lu Daru E-mail:drlu@fudan.edu.cn

摘要/Abstract

摘要： 为探讨人染色体8p11(CHRNB3-CHRNA6)区域基因多态性与中国汉族人群肺癌遗传易感性之间的关系, 文章采用病例-对照研究, 对784例肺癌患者和782例性别、年龄、籍贯频数与之相匹配的健康对照中该区域6个标签SNP位点进行基因分型, 并统计分析其基因型频率分布与肺癌易感性的关系, 以及吸烟在其中的影响。结果发现 rs16891561位点TT基因型在60岁以上人群(校正OR=0.42, 95% CI=0.20-0.88; P=0.022)、女性人群(校正OR=0.34, 95% CI=0.13-0.87; P=0.025)、非吸烟人群中(校正OR=0.32, 95% CI=0.13-0.79; P=0.013)对肺癌发生具有保护效应; rs4236926位点TT基因型在60岁以上人群(校正OR=0.48, 95% CI=0.23-0.99; P=0.048)、非吸烟人群(校正OR=0.32, 95% CI=0.13-0.80; P=0.014)中对肺癌发生具有保护效应, 这两种保护效应主要是与腺癌相关。对这两个位点进行累积效应分析发现, 含有3~4个变异等位基因型的非吸烟者罹患肺癌的风险显著降低(校正OR=0.29, 95% CI=0.11-0.71; P=0.007), 并且, 含有3~4个变异等位基因型的个体累计吸烟量 (“包-年”平均数=13.2)与其他个体相比显著降低。由此可见人染色体8p11(CHRNB3-CHRNA6)区域基因多态性与中国汉族人群肺癌易感性和吸烟行为相关。

关键词: CHRNB3, 8p11, CHRNA6, 单核苷酸多态性, 肺癌易感性

Abstract: To investigate the association between chromosome 8p11 (CHRNB3-CHRNA6) polymorphisms and lung cancer susceptibility in Chinese Han population, we genotyped 6 tag SNPs variants of this region among 784 patients with lung cancer and 782 age- and sex-matched cancer-free control participants to screen for any risk-associated SNPs. The results revealed that rs16891561 TT genotype had a protective effect against lung cancer in people over 60 years old (ad-justed OR=0.42, 95% CI=0.20-0.88; P=0.022), female groups (adjusted OR=0.34, 95% CI=0.13-0.87; P=0.025), and non-smoking people (adjusted OR=0.32, 95% CI=0.13-079; P=0.013). Additionally, rs4236926 TT genotype had a protective effect against lung cancer in people over 60 years old (adjusted OR=0.48, 95% CI=0.23-0.99; P=0.048) and non-smoking people (adjusted OR=0.32, 95% CI=0.13-0.80; P=0.014). According to pathological type of lung cancer, these two SNPs were associated with adenocarcinomas susceptibility. As to cumulative effect of rs4236926 and rs16891561, in non-smokers strata, lung cancer risk was significantly reduced in those who had 3-4 mutant alleles (adjusted OR=0.29, 95% CI=0.11-0.71; P=0.007). Furthermore, people containing 3-4 mutant alleles had lower level of smoking doses (mean pack-year=13.2) compared with others. In conclusion, 8p11 (CHRNB3-CHRNA6) polymorphisms are related to smoking behavior and lung cancer susceptibility in Chinese Han population.

Key words: 8p11, CHRNB3, CHRNA6, single nucleotide polymorphism, lung cancer susceptibility

张晓博，赵振宏，陈红岩，王久存，钱吉，杨亚军，魏庆义，黄建，卢大儒. 人染色体8p11(CHRNB3-CHRNA6)区域基因多态性与中国汉族人群肺癌易感性的相关性[J]. 遗传, 2011, 33(8): 886-894.

ZHANG Xiao-Bo, DIAO Zhen-Hong, CHEN Gong-Yan, WANG Jiu-Cun, JIAN Ji, YANG E-Jun, WEI Qiang-Xi, HUANG Jian, LEI Da-Ru. Human chromosome 8p11 (CHRNB3-CHRNA6) region gene polymorphisms and susceptibility to lung cancer in Chinese Han population[J]. HEREDITAS, 2011, 33(8): 886-894.

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人染色体8p11(CHRNB3-CHRNA6)区域基因多态性与中国汉族人群肺癌易感性的相关性

Human chromosome 8p11 (CHRNB3-CHRNA6) region gene polymorphisms and susceptibility to lung cancer in Chinese Han population

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