Association Of Genetic Polymorphisms At Five Sites Of TNF-? Promoter With Genetic Susceptibility To Cervical Cancer Of Han Population In Shandong Province

Objective To investigate the correlation between genotype and allele frequencies of 5single nucleotide polymorphisms(SNPs)in the promoter region of tumor necrosis factor-?(TNF-?)gene(rs361525,rs1800629,rs1800750,rs1799964 and rs673)and susceptibility of Cervical Cancer in Han Women in Shandong provence.Methods Four hundred and fifty-two patients with cervical cancer diagnosed by pathology were selected as cervical cancer group,including one hundred and four cases in situ cancer group and three hundred and fifty-eight cases in cervical invasive cancer group;Four hundred and ninty-four women selected for physical examination were used as control group.Both groups were Han women in Shandong.Firstly,an epidemiological survey was conducted for each group,including: general demographic characteristics,occupational exposure history,family history of tumors,and gestation status;Secondly,subtypes Human papilloma Virus(HPV)were detected in each group by polymerase chain reaction(PCR)+ diversion hybridization method;Lastly,Taq Man probe method was used to analyze and compare the gene types and gene frequencies of the five SNPs of TNF-? promoter in each group.Data were analyzed statistically using SPSS 17.0 software and Haploview 4.2 software.Results1.There was no significant difference in age,first marriage age,third parity and parity(P>0.05).There was significant difference between smoking and occupational exposure in carcinoma in situ and invasive cancer(P<0.05).2.The infection rate of high-risk HPV in cervical cancer group was 91.4%(413/452)which was higher than that in control group(10.3%)(51/494)(P<0.05);HR-HPV infection rate of the invasive cervical cancer group was95.4%(332/348),which was higher than that in cervical carcinoma in situ for77.9%(81/104).3.The rs361525(G/A),rs1800629(G/A),and rs1799964(C/T)genotypes of TNF-? gene promoter were different between the cervical cancer group and the control group(P<0.05);The rs1800750(G/A)and rs673(G/A)genotypes were not significantly different between the cervical cancer group and the control group(P>0.05).There were no significant differences in allelic types of SNP loci between invasive carcinoma and carcinoma in situ(P > 0.05).4.The frequency of A allele in rs361525 locus was 10.8% and 3.8% in cervical cancer group and control group,respectively(P<0.05).The genetic risk multiple was 3.040,95%CI:1.761~5.248;A allele frequency of rs1800629 was29.9% in the cervical cancer group and 14.2% in the control group(P<0.05).The genetic risk multiple of the A-allele-infected cervical cancer was2.580,95%CI:1.867~3.564;A allele frequency of rs1799964 was 38.3% in the cervical cancer group and 16.4% in the control group(P<0.05).The genetic risk multiple of cervical cancer in population was 3.162,95%CI: 2.332~4.287.Conclusions1.SNPs of TNF-? promoter,rs361525(AA + GA),rs1800629(AA + GA)and rs1799964(TT + TC),were related to the occurrence of cervical cancer in Han women in Shandong Province,which would be an important hint on diagnosis and prevention in gene level for cervical cancer patients;2.SNPs of TNF-? promoter,rs1800750(G/A)and rs673(G/A),were not significantly associated with cervical cancer in Han women in Shandong Province.3.The history of HR-HPV infection is the risk factor of cervical cancer,smoking and occupational exposure may be synergistic with the development of cervical cancer.