Department of Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shaghai Jiaotong University, 241 Huaihai West Road, Shanghai 200030, China.
J Thorac Oncol. 2010 May;5(5):658-66. doi: 10.1097/JTO.0b013e3181d5e447.
Recent genome-wide association studies in Caucasians revealed association with lung cancer risk of single nucleotide polymorphisms (SNPs) in the locus containing two nicotine acetylcholine receptor CHRNA genes. However, the reported risk SNPs are extremely rare in Asians. This study sought to identify other variants on CHRNA3 associated with lung cancer susceptibility and to explore whether SNPs of CHRNA3 are of prognostic factors in patients with non-small cell lung cancer (NSCLC) in Chinese Han population.
A case-control study of 529 cases and 567 controls was performed to study the association of three SNPs (rs3743076, rs3743078, and rs3743073) in CHRNA3 with lung cancer risk in Chinese Han population using logistic regression models. The relationship between CHRNA3 polymorphisms with overall survival among 122 patients with advanced stage (stage IIIb and IV) NSCLC were evaluated using Cox multiple model based on the International Association for the Study of Lung Cancer recommended tumor, node, metastasis new staging.
Patients with genotypes TG or GG for the novel SNP rs3743073 in CHRNA3 gene, compared with those with TT, showed an increased risk of lung cancer (adjusted odds ratio = 1.91; 95% confidence interval, 1.38-2.63; p = 9.67 x 10) and worst survival (adjusted hazard ratio = 2.35; 95% confidence interval, 1.05-5.26; p = 0.04) in patients with advanced stage NSCLC based on International Association for the Study of Lung Cancer recommended tumor, node, metastasis new staging.
These results suggest that the rs3743073 polymorphism in CHRNA3 is predictive for lung cancer risk and prognostic in advanced stage NSCLC in Chinese Han population.
最近在白种人群体中的全基因组关联研究揭示，位于包含两个尼古丁乙酰胆碱受体 CHRNA 基因的基因座中的单核苷酸多态性 (SNP) 与肺癌风险相关。然而，报告的风险 SNP 在亚洲人群中极为罕见。本研究旨在鉴定与肺癌易感性相关的 CHRNA3 上的其他变体，并探讨 CHRNA3 的 SNP 是否为中国汉族人群中非小细胞肺癌 (NSCLC) 患者的预后因素。
进行了一项病例对照研究，共纳入 529 例病例和 567 例对照，采用 logistic 回归模型研究 CHRNA3 中三个 SNP(rs3743076、rs3743078 和 rs3743073)与中国汉族人群肺癌风险的关系。采用 Cox 多模型基于国际肺癌研究协会推荐的肿瘤、淋巴结、转移新分期，评估 CHRNA3 多态性与 122 例晚期 (IIIb 期和 IV 期) NSCLC 患者总生存的关系。
与 TT 基因型相比，携带 CHRNA3 基因新 SNP(rs3743073)的 TG 或 GG 基因型的患者患肺癌的风险增加(调整后的优势比=1.91；95%置信区间，1.38-2.63；p=9.67 x 10)，且根据国际肺癌研究协会推荐的肿瘤、淋巴结、转移新分期，晚期 NSCLC 患者的生存最差(调整后的危险比=2.35；95%置信区间，1.05-5.26；p=0.04)。
这些结果表明，CHRNA3 中的 rs3743073 多态性与中国汉族人群中晚期 NSCLC 的肺癌风险和预后相关。
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