| Objective:Cervical Cancer(CC)is the second most common malignant tumor for women in our country,that serious threat women’s health and safety.High-risk human papilloma virus(HR-HPV)persistent infection is considered to be the main cause of cervical cancer.Most of the patients infected with HPV can be cleared by the host immune system.Only a small part of the population will continue infected,can further develop into cervical intraepithelial neoplasia(CIN),and even progress to cervical cancer.Whether HPV infection will develop into intraepithelial neoplasia or cervical cancer is related to many factors,among which the genetic susceptibility of the host is one of the important reasons.Tumor necrosis factor(TNF)is a pro-inflammatory cytokine with multiple biological activities,including two types:tumor necrosis factor-α(TNF-α)and tumor necrosis factor-β(TNF-β).TNF-α is mainly produced by monocytes/macrophages,and can play the role of oncogene and tumor suppressor gene in human immune responses.The polymorphism of human TNF-α is mainly concentrated in the promoter region,and its polymorphism is closely related to the expression of TNF-α and the risk of a variety of diseases.This study selected five SNPs located in the promoter region of the TNF-α gene:rs 1799964(C>T),rs1800630(A>C),rs1799724(C>T),rs1800629(A>G),rs361525(A>G)to explore the distribution of alleles and genotypes of these five SNPs in intraepithelial neoplasia,cervical cancer and healthy populations of Han population in Yunnan Province,aimed at clarify the role of gene polymorphisms at the SNPs site on the TNF-α gene promoter in the occurrence and development of cervical cancer.Methods:A total of 2,372 subjects in this study,including:1,173 healthy controls,579 patients with CIN,and 980 patients with CC;and according to clinical pathological data,patients with CC were divided into different types(squamous cell carcinoma(SCC),Adenocarcinoma(AC),other types(Other)).Use the TaqMan Assay genotyping method to genotype the five SNPs of the research object;X2 test was used to analyze the differences in genotypes and allele distribution frequencies of five SNPs;SHEsis program was used to calculate the Hardy-Weinberg equilibrium,locus linkage disequilibrium and haplotype between the five SNPs;SNPStats software was used to analyze the five SNPs under different genetic modes.Results:1.The results of genotype and allele analysis showed:comparing the CC group with the Control group,the A allele of rs1800629 is a protective factor of CC(P=0.009,OR=0.722;95%CI=0.564-0.923).The A allele of rs361525 is a risk factor for the occurrence of CC(P=0.002,OR=1.693;95%CI=1.205-2.378).In addition,the genotype frequency of rs361525 is also different(P=0.009).In the comparison between the CIN group and the Control group,there was no statistical difference in the five sites(P>0.01).Subgroup analysis showed:compared the SCC group with the Control group,the A allele of rs1800629 is a protective factor of SCC(P=0.002,OR=0.659;95%CI=0.502-0.864).In addition,the genotype frequency of rs1800629 is also difference(P=0.006);the A allele of rs361525 is a risk factor of SCC(P<0.01,OR=1.868;95%CI=1.317-2.648).Comparing AC group and Other group with Control group,there was no statistical difference in the five sites(P>0.01)2:The results of genetic pattern analysis showed:Comparing the CC group with the Control group,the dominant inheritance pattern is the optimal pattern of rs1800630.In this model,the A/C-A/A genotype is related to the reduced risk of CC(P=0.006,OR=0.77;95%CI=0.64-0.93).The overdominant inheritance model is the optimal model of rs1800629.In this model,the A/G genotype is related to the reduced risk of CC(P=0.008,OR=0.70;95%CI=0.53-0.91).The dominant inheritance model is the optimal model of rs361525.In this model,the A/G-A/A genotype is related to the increased risk of CC(P=0.008,OR=1.63;95%CI=1.14-2.35).Subgroup analysis showed:compared the SCC group with the Control group,the overdominant inheritance model is the optimal model of rs1800629.In this model,the A/G genotype is related to the reduced risk of SCC(P=0.002,OR=0.63;95%CI=0.47-0.84).The dominant inheritance model is the optimal model of rs361525.In this model,the A/G-A/A genotype is related to the increased risk of SCC(P=0.002,OR=1.80;95%CI=1.24-2.61).3:The results of haplotype analysis showed:Comparing the CIN group and the Control group,the haplotype rs1799724C-rs 1800629A may be a protective factor for CIN(P=0.016,OR=0.694;95%CI=0.515-0.936);the haplotype rs1799724C-rs1800629G may be caused by CIN risk factors(P=0.012,OR=1.279;95%CI=1.055-1.551).Compared with the Control group,the haplotype rs1799964C-rs1800630A may be a protective factor for the occurrence of CC(P=0.005,OR=0.825;95%CI=0.707-0.963);the haplotype rs1799964C-rs1800630C may be caused by CC risk factors(P=0.005,OR=1.596;95%CI=1.145-2.225);haplotype rs1799724C-rs 1800629A may be a protective factor for the occurrence of CC(P=0.011,OR=0.725;95%CI=0.567-0.928).Subgroup analysis showed:Compared the SCC group and the Control group,the haplotype rs1799964C-rs1800630C may be a risk factor for SCC(P<0.001,OR=1.814;95%CI=1.292-2.546).The haplotype rs1799724C-rs1800629A may be a protective factor for the occurrence of SCC(P=0.003,OR=0.661;95%CI=0.504-0.868).Conclusions:The rs1800629 and rs361525 in the TNF-α gene promoter are related to the susceptibility of cervical cancer to squamous cell carcinoma in the Chinese Han population. |
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