Background: Hypoxia inducible factor-1α (HIF-1α) is associated with the progression and metastasis of lung cancer. There are, however, few studies on the relationship between the single nucleotide polymorphisms of HIF-1α and susceptibility to lung cancer. Therefore, we aimed to investigate the relationship between indoor air pollution, HIF-1α rs2057482, and the susceptibility to primary lung cancer of the Fujian Han population.
Methods: The present study is a hospital-based case-control study. We recruited 1,096 lung cancer and 1,110 controls that were admitted to the Department of Thoracic Surgery of the First Affiliated Hospital and Union Hospital of Fujian Medical University and Fuzhou General Hospital of Nanjing Military Region from January 2006 to December 2012. The primary lung cancer cases were identified via pathological methods. Both case and control groups received questionnaires. Genotyping of HIF-1α gene rs2057482 locus polymorphism in all subjects were analyzed by MALDI-TOF-MS technique.
Results: Individuals who carried the T-genotype of HIF-1α rs2057482 were more susceptible to small cell carcinoma (odds ratio of 1.725, 95%CI: 1.047-2.842). After adjusting for general and lung cancer-related factors, we found that in the co-dominant genetic model, rs2057482 TT carriers were 2.195 times more likely to develop lung cancer than CC carriers (95%CI: 1.038-4.463) in the population that were exposed to passive smoking. In the dominant genetic model, the risk of lung cancer was 1.911 times (95%CI: 1.121-3.258) that in the carriers of the rs2057482 T allele with a family history of cancer. In the recessive genetic model, rs2057482 TT carriers had a 0.159-fold increased risk of lung cancer (95%CI: 0.028-0.920) than TC+CC carriers in people with a history of lung disease. In the additive genetic model, the risk of lung cancer in rs2057482 TC+TT carriers was 1.542 times (95%CI: 1.107-2.340) that in the CC family of people with a family history of cancer.
Conclusions: HIF-1α rs2057482 may be associated with lung cancer susceptibility. .
背景与目的 低氧诱导因子-1α（hypoxia inducible factor 1α, HIF-1α）与肺癌的恶化与转移有关，但HIF-1α的单核苷酸多态性（single nucleotide polymorphisms, SNPs）与肺癌易感性的研究仍较少。本研究旨在探讨室内空气污染、rs2057482多态性与福建汉族肺癌易感性的关系。方法 采用以医院为基础的病例对照设计，选择2006年1月-2012年12月在福建医科大学附属第一医院、协和医院和南京军区福州总医院的胸外科及呼吸内科病理确诊的汉族新发原发性肺癌患者1,096例，选取无肿瘤病史、同期前往医院其他科室探视的患者汉族亲友和社区汉族人群1,110例，进行问卷调查。应用MALDI-TOF-MS技术对所有研究对象HIF-1α基因rs2057482位点多态性进行基因分型。结果 携带有HIF-1α rs2057482位点T基因型的人群更容易罹患小细胞癌［TT vs CC的比值比（odds ratio, OR）值为1.725，95%CI：1.047-2.842］。调整一般情况和肺癌有关影响因素后，在共显性遗传模型中，暴露于被动吸烟的rs2057482 TT携带者肺癌患病风险是CC携带者的2.195倍（95%CI: 1.038-4.643）。在显性遗传模型中，有肿瘤家族史的rs2057482 T基因携带者肺癌患病风险是C基因携带者的1.911倍（95%CI: 1.121-3.258）。在隐性遗传模型中，肺部疾病史的rs2057482 TT携带者的肺癌患病风险是TC+CC携带者的0.159倍（95%CI: 0.028-0.920）。在加性遗传模型中，有肿瘤家族史的rs2057482 TC+TT携带者的肺癌患病风险是CC携带者的1.542倍（95%CI: 1.107-2.340）。结论 HIF-1α rs2057482位点可能与肺癌易感性存在一定关联。.