室内空气污染、HIF-1α基因单核苷酸多态性与福建汉族肺癌易感性的关系
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摘要
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-1αrs2057482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-1αrs2057482位点可能与肺癌易感性存在一定关联。
Background and objective 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 topassive 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. Conclusion HIF-1α rs2057482 may be associated with lung cancer susceptibility.
Background and objective 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 topassive 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. Conclusion HIF-1α rs2057482 may be associated with lung cancer susceptibility.
引文
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6 Liu ZQ,He F,Lin Y,et al.A case-control study on the relationship between living environment and indoor air pollution and lung cancer.Zhongguo Gong Gong Wei Sheng,http://www.cnki.net/kcms/detail/21.1234R.20160906.1525.070.html.[刘志强,何斐,林勇,等.居住环境及室内空气污染与肺癌发病关系病例对照研究.中国公共卫生,http://www.cnki.net/kcms/detail/21.1234.R.20160906.1525.070.html]
7 Hu M,Xiao XL,Liu Y,et al.Research progress on hypoxia-inducible factor 1α.Yi Xue Zong Shu,2006,12(21):1283-1285.[胡明,肖新莉,刘勇,等低氧诱导因子-1研究进展.医学综述,2006,12(21):1283-1285.]
8 Liu YV,Baek JH,Zhang H,et al.RACK1 competes with HSP90 for binding to HIF-1αand is required for O(2)-independent and HSP90 inhibitorinduced degradation of HIF-1α.Mol Cell,2007,25(2):207-217.
9 Jeong JK,Moon MH,Seo JS,et al.Hypoxia inducing factor-1αregulates tumor necrosis factor-related apoptosis-inducing ligand sensitivity in tumor cells exposed to hypoxia.Biochem Biophys Res Commun,2010,399(3)379-383.
10 Lve Y,Zhang P.Research progress of HIF-1αand its relationship with lung cancer.Zhongguo Fei Ai Za Zhi,2009,12(2):147-151.[吕扬,张鹏.HIF 1α的研究进展及与肺癌的关系.中国肺癌杂志,2009,12(2):147-151.]
11 Wan J,Wu W,Chen Y,et al.Insufficient radiofrequency ablation promotes the growth of non-small cell lung cancer cells through PI3K/Akt/HIF-1αsignals.Acta Biochim Biophys Sin(Shanghai),2016,48(4):371-377.
12 Qian J,Bai H,Gao Z,et al.Downregulation of HIF-1αinhibits the proliferation and invasion of non-small cell lung cancer NCI-H157 cells Oncol Lett,2016,11(3):1738-1744.
13 Li XB,You JC,Zhou QH.Advances in hypoxia and lung cancer.Zhongguo Fei Ai Za Zhi,2013,16(4):216-220.[李雪冰,尤嘉琮,周清华.低氧与肺癌的研究进展.中国肺癌杂志,2013,16(4):216-220.]
14 Wang X,Ren H,Zhao T,et al.Single nucleotide polymorphism in the micro RNA-199a binding site of HIF1A gene is associated with pancreatic ductal adenocarcinoma risk and worse clinical outcomes.Oncotarget,20167(12):13717-13729.
15 Fu SL,Miao J,Ding B,et al.A polymorphism in the 3'untranslated region o hypoxia-inducible factor-1 alpha confers an increased risk of cervical cancer in a Chinese population.Neoplasma,2014,61(1):63-69.
16 Li P,Cao Q,Shao PF,et al.Genetic polymorphisms in HIF1A are associated with prostate cancer risk in a Chinese population.Asian J Androl,201214(6):864-869.
17 Qin C,Cao Q,Ju X,et al.The polymorphisms in the VHL and HIF1A genes are associated with the prognosis but not the development of renal cel carcinoma.Ann Oncol,2011,23(4):981-989.
18 Zhang Y,Wang P,Zhou XC,et al.Genetic variations in the HIF1A gene modulate response to adjuvant chemotherapy after surgery in patients with colorectal cancer.Asian Pac J Cancer Prev,2014,15(11):4637-4642.
19 Guo X,Li D,Chen Y,et al.SNP rs2057482 in HIF1A gene predicts clinica outcome of aggressive hepatocellular carcinoma patients after surgery.Sc Rep,2015,5:11846.
20 Zhang Q,Tang X,Zhang ZF,et al.Nicotine induces hypoxia-inducible factor-1αexpression in human lung cancer cells via nicotinic acetylcholine receptor-mediated signaling pathways.Clin Cancer Res,2007,13(16)4686-4694.
21 Guo L,Li L,Wang W,et al.Mitochondrial reactive oxygen species mediates nicotine-induced hypoxia-inducible factor-1αexpression in human nonsmall cell lung cancer cells.Biochim Biophys Acta,2012,1822(6):852-861.
2 Hu Y,Li BL.Advances in studies of hypoxia-inducible factor-1αand 2αin malignant tumors.Ai Zheng Jin Zhan,2014,12(2):122-125.[胡瑛,李宝兰缺氧诱导因子-1α、2α在恶性肿瘤中不同作用的研究进展.癌症进展,2014,12(2):122-125.]
3 Qian J,Bai H,Gao Z,et al.Downregulation of HIF-1αinhibits the proliferation and invasion of non-small cell lung cancer NCI-H157 cells Oncol Lett,2016,11(3):1738-1744.
4 He J,Hu Y,Hu M,et al.The relationship between the preoperative plasma level of HIF-1αand clinic pathological features,prognosis in non-small cel lung cancer.Sci Rep,2016,6:20586.
5 He F,Lin JB,Yu TT,et al.Interaction research on smoking and micro RNAgenes SNP related to lung cancer in Fujian Han population.Zhonghua Yu Fang Yi Xue Za Zhi,2016,63(2):168-174.[何斐,林剑波,俞婷婷,等.福建省汉族人群肺癌相关micro RNA基因SNP与吸烟交互作用研究.中华预防医学杂志,2016,63(2):168-174.]
6 Liu ZQ,He F,Lin Y,et al.A case-control study on the relationship between living environment and indoor air pollution and lung cancer.Zhongguo Gong Gong Wei Sheng,http://www.cnki.net/kcms/detail/21.1234R.20160906.1525.070.html.[刘志强,何斐,林勇,等.居住环境及室内空气污染与肺癌发病关系病例对照研究.中国公共卫生,http://www.cnki.net/kcms/detail/21.1234.R.20160906.1525.070.html]
7 Hu M,Xiao XL,Liu Y,et al.Research progress on hypoxia-inducible factor 1α.Yi Xue Zong Shu,2006,12(21):1283-1285.[胡明,肖新莉,刘勇,等低氧诱导因子-1研究进展.医学综述,2006,12(21):1283-1285.]
8 Liu YV,Baek JH,Zhang H,et al.RACK1 competes with HSP90 for binding to HIF-1αand is required for O(2)-independent and HSP90 inhibitorinduced degradation of HIF-1α.Mol Cell,2007,25(2):207-217.
9 Jeong JK,Moon MH,Seo JS,et al.Hypoxia inducing factor-1αregulates tumor necrosis factor-related apoptosis-inducing ligand sensitivity in tumor cells exposed to hypoxia.Biochem Biophys Res Commun,2010,399(3)379-383.
10 Lve Y,Zhang P.Research progress of HIF-1αand its relationship with lung cancer.Zhongguo Fei Ai Za Zhi,2009,12(2):147-151.[吕扬,张鹏.HIF 1α的研究进展及与肺癌的关系.中国肺癌杂志,2009,12(2):147-151.]
11 Wan J,Wu W,Chen Y,et al.Insufficient radiofrequency ablation promotes the growth of non-small cell lung cancer cells through PI3K/Akt/HIF-1αsignals.Acta Biochim Biophys Sin(Shanghai),2016,48(4):371-377.
12 Qian J,Bai H,Gao Z,et al.Downregulation of HIF-1αinhibits the proliferation and invasion of non-small cell lung cancer NCI-H157 cells Oncol Lett,2016,11(3):1738-1744.
13 Li XB,You JC,Zhou QH.Advances in hypoxia and lung cancer.Zhongguo Fei Ai Za Zhi,2013,16(4):216-220.[李雪冰,尤嘉琮,周清华.低氧与肺癌的研究进展.中国肺癌杂志,2013,16(4):216-220.]
14 Wang X,Ren H,Zhao T,et al.Single nucleotide polymorphism in the micro RNA-199a binding site of HIF1A gene is associated with pancreatic ductal adenocarcinoma risk and worse clinical outcomes.Oncotarget,20167(12):13717-13729.
15 Fu SL,Miao J,Ding B,et al.A polymorphism in the 3'untranslated region o hypoxia-inducible factor-1 alpha confers an increased risk of cervical cancer in a Chinese population.Neoplasma,2014,61(1):63-69.
16 Li P,Cao Q,Shao PF,et al.Genetic polymorphisms in HIF1A are associated with prostate cancer risk in a Chinese population.Asian J Androl,201214(6):864-869.
17 Qin C,Cao Q,Ju X,et al.The polymorphisms in the VHL and HIF1A genes are associated with the prognosis but not the development of renal cel carcinoma.Ann Oncol,2011,23(4):981-989.
18 Zhang Y,Wang P,Zhou XC,et al.Genetic variations in the HIF1A gene modulate response to adjuvant chemotherapy after surgery in patients with colorectal cancer.Asian Pac J Cancer Prev,2014,15(11):4637-4642.
19 Guo X,Li D,Chen Y,et al.SNP rs2057482 in HIF1A gene predicts clinica outcome of aggressive hepatocellular carcinoma patients after surgery.Sc Rep,2015,5:11846.
20 Zhang Q,Tang X,Zhang ZF,et al.Nicotine induces hypoxia-inducible factor-1αexpression in human lung cancer cells via nicotinic acetylcholine receptor-mediated signaling pathways.Clin Cancer Res,2007,13(16)4686-4694.
21 Guo L,Li L,Wang W,et al.Mitochondrial reactive oxygen species mediates nicotine-induced hypoxia-inducible factor-1αexpression in human nonsmall cell lung cancer cells.Biochim Biophys Acta,2012,1822(6):852-861.