课题背景：本研究经复旦大学生命科学学院伦理委员会批准,通过对新发肺癌患者; 无其他器官恶性肿瘤史; 无性别、年龄及病理类型的限制, 共784 例患者作为实验组。自同一时期相应社区健康体检者,其籍贯分布地区(城乡)、性别、年龄(±5 岁)与病例频数匹配, 共782 例作为对照组进行研究。（注：所有人群均为汉族人群）来寻找出染色体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。

研究方法：通过HapMap 数据库Ⅱ期数据, 设置最小等位基因频率(Minor allele frequency, MAF)≥0.05, 关联强度r2≥0.8。来在染色体8p11 区从42 671 719 bp 到42 742 776 bp共71 kb 区域内选取6 个tag SNP。接下来对样本进行DNA提取，由上海天昊公司采用连接酶检测反应(Ligase detectionreaction, LDR)原理进行基因分型。对其进行统计分析（其中应用了卡方检验，Haploview软件，χ2 检验，Logistic 回归）。

研究结果：rs16891561 位点TT 基因型在60 岁以上人群、女性人群、非吸烟人群中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、非吸烟人群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。并且含有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,含有3~4 个变异等位基因型的个体累计吸烟量与其他个体相比显著降低。证明人染色体8p11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。

参考文献： Abstract: To investigate the association between chromosome 8p11 (CHRNB3-CHRNA6) polymorphisms and lung cancersusceptibility in Chinese Han population, we genotyped 6 tag SNPs variants of this region among 784 patients with lungcancer and 782 age- and sex-matched cancer-free control participants to screen for any risk-associated SNPs. The resultsrevealed that rs16891561 TT genotype had a protective effect against lung cancer in people over 60 years old (adjustedOR=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-smokingpeople (adjusted OR=0.32, 95% CI=0.13-079; P=0.013). Additionally, rs4236926 TT genotype had a protective effectagainst 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 wereassociated with adenocarcinomas susceptibility. As to cumulative effect of rs4236926 and rs16891561, in non-smokersstrata, 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.

Keywords: 8p11; CHRNB3; CHRNA6; single nucleotide polymorphism; lung cancer susceptibility