中国癌症杂志 ›› 2021, Vol. 31 ›› Issue (7): 616-628.doi: 10.19401/j.cnki.1007-3639.2021.07.008

• 论著 • 上一篇    下一篇

云南省汉族人群TNF-α基因多态性与非小细胞肺癌发生、发展的相关性

杨 佳 1 ,刘舒媛 1 ,王莹莹 1 ,李盈甫 2 ,马千里 3 ,李 玙 1 ,王永蓉 1 ,李传印 1 ,谭 芳 2   

  1. 1. 中国医学科学院北京协和医学院医学生物学研究所,云南省重大传染病疫苗研发重点实验室,
     云南 昆明 650118 ;
    2. 昆明医科大学第一附属医院干部医疗科,云南 昆明 650032 ;
    3. 昆明医科大学第三附属医院胸外科,云南 昆明 650118
  • 出版日期:2021-07-30 发布日期:2021-08-04
  • 通信作者: 谭 芳 E-mail: tanfang626@126.com
  • 基金资助:
    国家自然科学基金(81573206);云南省应用基础研究计划(2016FA034);中国医学科学院重大协同创新项目(2016-I2M-2-001);云南省应用基础研究计划-昆明医科大学联合专项[2017FE468(-193),2018FE001(-219)]。

The association of polymorphisms in TNF-α gene with non-small cell lung cancer in Han population of Yunnan Province 

YANG Jia 1 , LIU Shuyuan 1 , WANG Yingying 1 , LI Yingfu 2 , MA Qianli 3 , LI Yu 1 , WANG Yongrong 1 , LI Chuanyin 1 , TAN Fang   

  1. 1. Key Laboratory for Research and Development of Major Infectious Diseases Vaccine in Yunnan, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming 650118, Yunnan Province, China; 2. Department of Cadre Medicine, the First Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan Province, China; 3. Department of Thoracic Surgery, the Third Affiliated Hospital of Kunming Medical University, Kunming 650118, Yunnan Province, China
  • Published:2021-07-30 Online:2021-08-04
  • Contact: TAN Fang E-mail: tanfang626@126.com

摘要: 背景与目的:肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)不仅是一种重要的炎症因子,还与肿瘤的发生、发展密切相关。探讨TNF-α基因多态性与云南省汉族人群非小细胞肺癌(non-small cell lung cancer,NSCLC)发生、发展的相关性。方法:选取云南省425例汉族人群NSCLC病例和438名健康体检者,采用TaqMan探针基因分型法对TNF-α基因启动子区域5个单核苷酸多态性(single nucleotide polymorphism,SNP)位点rs1799964(-1031T>C)、rs1800630(-863C>A)、rs1799724(-857C>T)、rs1800629(-308G>A)和rs361525(-238G>A)进行基因分型并分析其等位基因、基因型及所构建的单倍型在NSCLC病例及健康对照者中的频率差异。结果:TNF-α基因启动子5个SNP位点的等位基因和基因型频率在NSCLC病例组和对照组间差异无统计学意义(P>0.05)。病例分层分析发现,rs1799724(C>T)的T等位基因在腺癌组中的频率显著高于对照组(P=0.010,OR=1.56,95% CI:1.11~2.19),在显性模式下携带T等位基因的个体(TT+CT)患肺腺癌的风险显著升高(P=0.007,OR=1.66,95% CI:1.15~2.42)。rs1800630(C>A)的A等位基因在腺鳞癌及其他类型肺癌组中的频率显著高于对照组,差异有统计学意义(P=0.013,OR=2.15,95% CI:1.16~3.96)。单倍型分析结果显示,单倍型rs1799724T-rs1800629G在腺癌组中的频率显著高于对照组(P=0.048,OR=1.42,95% CI:1.00~2.01)。结论:位于TNF-α基因启动子区域的SNP位点rs1799724(C>T)等位基因T和基因型TT可能是云南省汉族人群NSCLC中腺癌发生的风险性因素。SNP位点rs1800630(C>A)等位基因A可能是云南省汉族人群NSCLC中腺鳞癌及其他类型肺癌发生的风险性因素。

关键词: 非小细胞肺癌, 肿瘤坏死因子-α, 单核苷酸多态性, 相关性, 云南省汉族人群

Abstract: Background and purpose: Tumor necrosis factor-α (TNF-α) not only acts as proinflammatory cytokine conducing to wide spectrum of human diseases including inflammatory diseases, but also can induce tumor development. In the current study, we investigated the relationship between TNF-α gene polymorphisms and the occurrence and development of non-small cell lung cancer (NSCLC) in Han population of Yunnan Province. Methods: A total of 425 lung cancer patients with NSCLC and 438 healthy individuals were included from Han population of Yunnan Province. The genotypes of 5 polymorphism loci, rs1799964 (-1031T>C), rs1800630 (-863C>A), rs1799724 (-857C>T), rs1800629 (-308G>A) and rs361525 (-238G>A) of TNF-α gene were detected by TaqMan assay. The frequency distributions of allele, genotype and haplotype in NSCLC patients and healthy controls were analyzed. Results: There was no significant difference in the allele and genotype frequency among 5 single nucleotide polymorphism (SNP) sites in TNF-α gene promoter (P>0.05). And in stratification analysis, the frequency of rs1799724-T was significantly higher in the adenocarcinoma patients than in the controls (P=0.010, OR=1.56, 95% CI: 1.11-2.19), and the rs1799724-TT+TC carrier showed significantly higher susceptibility to adenocarcinoma in dominant model (P=0.007, OR=1.66, 95% CI: 1.146-2.417). The frequency of rs1800630-A was significantly higher in adenocarcinoma, squamous cell carcinoma and other histological types of carcinoma patients (P=0.013, OR=2.15, 95% CI: 1.16-3.96). The haplotype analysis indicated that the frequency of haplotype rs1799724T-rs1800629G was higher in the adenocarcinoma group than in the control group (P=0.048, OR=1.42, 95% CI: 1.00-2.01). Conclusion: The T allele and TT genotype of rs1799724 (C>T) in TNF-α gene promoter might be associated with the susceptibility to lung adenocarcinoma in Han population of Yunnan Province. And rs1800630 (C>T) -A might be a risk factor of other histological lung cancer in Han population of Yunnan Province.

Key words: Non-small cell lung cancer, Tumor necrosis factor-α, Single nucleotide polymorphism, Association, Han population of Yunnan Province