摘要
目的探讨肿瘤坏死因子-α(tumor necrosis factorα,TNF-α)基因位点rs1800629单核苷酸多态性与宫颈癌发生的关系。方法选择经组织学确诊的汉族552例新发宫颈癌患者作为病例组,与病例组人群不存在生物学相关的654例正常人群作为对照组,利用Taqman实时荧光定量聚合酶链式反应(polymerase chain reaction,PCR)技术检测基因型,Logistic回归模型计算基因型与人群罹患宫颈癌的风险比(odds ratio,OR)及其95%的可信区间(95%CI); Stata 11. 0软件对中国人群rs1800629多态性与宫颈癌的关系进行Meta分析。结果与TNF-αrs1800629野生型GG基因型的相比,个体携带rs1800629 GA、AA及GA/AA基因型的个体罹患宫颈癌的风险差异无统计学意义(均有P> 0. 05);对该位点多态性与宫颈癌关系的Meta分析发现,TNF-αrs1800629遗传变异与中国人群宫颈癌的发生无明显相关性。结论 TNF-α基因rs1800629位点多态性可能与中国人群宫颈癌发生无关。
Objective To investigate the relationship between tumor necrosis factor α( TNF-αrs1800629 polymorphisms and cervical cancer risk. Methods A case-control study was carried out including 552 patients with cervical cancer and 654 normal controls during the same period. TNF-αrs1800629 polymorphisms were examined by Taqman-Probe assay method. The association between the genotypes and cervical cancer was analyzed by Logistic regression models. Stata 11. 0 was used for the Meta-analysis. Results Compared with the TNF-α rs1800629 GG genotype,individuals with GA,AA and GA/AA genotypes showed no significant changes in the risk of cervical cancer( all P > 0. 05). Further Meta-analysis on the relationship between the polymorphisms of TNF-α rs1800629 and cervical cancer also suggested that there was no significant correlation between the genetic variation and the occurrence of cervical cancer. Conclusion The polymorphisms of TNF-α rs1800629 may not be related to cervical cancer risk in Chinese population.
引文
[1]Bosch FX.The path to eliminate cervical cancer in the world and the challenges of professional education.Preface[J].Vaccine,2013,31(Suppl 6):4-5.DOI:10.1016/j.vaccine.2013.10.007
[2]Li J,Kang LN,Qiao YL.Review of the cervical cancer disease burden in mainland China[J].Asian Pac J Cancer Prev,2011,12(5):1149-1153.DOI:10.1097/01.cad.0000390767.85658.83.
[3]Danaei G,Vander Hoorn S,Lopez AD,et al.Causes of cancer in the world:comparative risk assessment of nine behavioural and environmental risk factors[J].Lancet,2005,366(9499):1784-1793.DOI:10.1016/s0140-6736(05)67725-2.
[4]Shishodia S,Majumdar S,Banerjee S,et al.Ursolic acid inhibits nuclear factor-κB activation induced by carcinogenic agents through suppression of IκBαkinase and p65 phosphorylation[J].Cancer Res,2003,63(15):4375-4383.DOI:10.1136/jnnp.2008.148429.
[5]Du GH,Wang JK,Richards JR,et al.Genetic polymorphisms in tumor necrosis factor alpha and interleukin-10 are associated with an increased risk of cervical cancer[J].Int Immunopharmacol,2019,66:154-161.DOI:10.1016/j.intimp.2018.11.015.
[6]Wang Q,Zhang C,Walayat S,et al.Association between cytokine gene polymorphisms and cervical cancer in a Chinese population[J].Eur J Obstet Gynecol Reprod Biol,2011,158(2):330-333.DOI:10.1016/j.ejogrb.2011.05.019.
[7]Wang N,Yin D,Zhang S,et al.TNF-Alpha rs1800629 polymorphism is not associated with HPV infection or cervical cancer in the Chinese population[J].PLo S One,2012,7(9):e45246.DOI:10.1371/journal.pone.0045246.
[8]Li X,Yin G,Li J,et al.The correlation between TNF-αpromoter gene polymorphism and genetic susceptibility to cervical cancer[J].Technol Cancer Res Treat,2018,17:1533033818782793.DOI:10.1177/1533033818782793.
[9]Li LP,Liu J,Liu CJ,et al.The correlation between TNF-α-308gene polymorphism and susceptibility to cervical cancer[J].Oncol Lett,2018,15(5):7163-7167.DOI:10.3892/ol.2018.8246.
[10]祖菲娅·艾力,艾星子·艾里,拉莱·苏祖克,等.肿瘤坏死因子基因多态性与新疆南部地区维吾尔族妇女子宫颈癌相关性研究[J].现代妇产科进展,2010,19(9):684-687,691.DOI:10.13283/j.cnki.xdfckjz.2010.09.024.Zufeiya·Aili,Aixingzi·Aili,Lalai·Suzuke,et al.Gene polymorphisms of tumor necrosis factor and the susceptibility to cervical cancer in Uighur population in Southern Xinjiang[J].Progress in Obstetrics&Gynecology,2010,19(9):684-687,691.DOI:10.13283/j.cnki.xdfckjz.2010.09.024.
[11]黄丽丽,许礼发.细胞因子基因型多态性与HPV引起的子宫颈损伤相关性研究[J].蚌埠医学院学报,2012,37(7):783-784,787.DOI:10.13898/j.cnki.issn.1000-2200.2012.07.034.Huang LL,Xu LF.Research of gene polymorphism of cytokines on human papilloma virus induced cervical injury[J].Journal of Bengbu Medical College,2012,37(7):783-784,787.DOI:10.13898/j.cnki.issn.1000-2200.2012.07.034.
[12]Kunita A,Baeriswyl V,Meda C,et al.Inflammatory cytokines induce podoplanin expression at the tumor invasive front[J].Am JPathol,2018,188(5):1276-1288.DOI:10.1016/j.ajpath.2018.01.016.
[13]陈谦,仇小强.基于大数据对宫颈癌缺氧生物标志物的分析[J].中华疾病控制杂志,2017,21(5):496-500.DOI:10.16462/j.cnki.zhjbkz.2017.05.016.Chen Q,Qiu XQ.Bioinformatics analysis of hypoxic markers in cervical cancer via big data[J].Chin J Dis Control Prev,2017,21(5):496-500.DOI:10.16462/j.cnki.zhjbkz.2017.05.016.
[14]Katan SA,Hisham YMA,Jaladet MSJ.Concentration levels of IL-10 and TNFαcytokines in patients with human papilloma virus(HPV)DNA+and DNA cervical lesions[J].J Immunotoxicol,2012,9(2):168-172.DOI:10.3109/1547691X.2011.642419.
[15]Nieves-Ramirez ME,Partida-Rodriguez O,Alegre-Crespo PE,et al.Characterization of single-nucleotide polymorphisms in the tumor necrosis factorαpromoter region and in lymphotoxinαin squamous intraepithelial lesions,precursors of cervical cancer[J].Transl Oncol,2011,4(6):336-344.DOI:10.1593/tlo.11226.
[16]Das CR,Tiwari D,Dongre A,et al.Deregulated TNF-Alpha levels along with HPV genotype 16 infection are associated with pathogenesis of cervical neoplasia in Northeast Indian patients[J].Viral Immunol,2018,31(4):282-291.DOI:10.1089/vim.2017.0151.
[17]Powell CB,Scott JH,Collins JL.Comparison of TNFalpha and TNFbeta cytolytic mechanisms in human ovarian and cervical carcinoma cell lines[J].Gynecol Oncol,1998,71(2):258-265.DOI:10.1006/gyno.1998.5178.
[18]Ding B,Fu S,Wang M,et al.Tumor necrosis factorα-308 G>A polymorphisms and cervical cancer risk:a Meta-analysis[J].Int J Gynecol Cancer,2012,22(2):213-219.DOI:10.1097/IGC.0b013e3182375aed.
[19]Wang LL,Ma KP,Wang ZY,et al.Association between tumor necrosis factor alpha rs1800629 polymorphism and risk of cervical cancer[J].Int J Clin Exp Med,2015,8(2):2108-2117.