Correlation Between HTERT Gene Polymorphism And Susceptibility To HPV In Cervical Cancer And Precancerous Lesions

Objectives:Investigating the prevalence of cervical precancerous lesions and cervical cancer with HPV infection in patients.To study the effection of single nucleotide polymorphism of hTERT gene in the development of cervical cancer.And exploring the relationship between hTERT gene single nucleotide polymorphism and HPV infection,single type infection and polytype infection,different subtype infections.Methods:Samples of cervical tissue from Yunnan Cancer Hospital(the third affiliated hospital of Kunming Medical University)from January 2015 to December 2017 were collected,including 70 cases of normal cervical group,64 cases of cervical precancerous lesions and 99 cases of cervical cancer.HPV detection and typing by PCR-membrane hybridization,the HPV virus infection rate between groups was compared;the difference between HPV monotype infection and polymorphic infection,and the HPV 16 infection and non-HPV 16 infection rate Case.The Taq Man probe was used to detect three groups of hTERT genes.The known 9 loci were rs2853691(C>T),rs2736122(G>A),rs10069690(C>T),rs2853676(C>T),rs2853677(A>G),rs2075786(A>G),rs2736098(C>T),rs2853690(A>G)and rs2736114(C>T)single nucleotide polymorphisms,comparing the single nucleotides of the 9 sites of the hTERT gene Relationship between HPV infection,single-type infection and polymorphic infection,HPV 16 infection and non-HPV 16 infection.Results:1 HPV infection1.1 The HPV infection rate was 67.2%in cervical precancerous lesions and 92.9%in cervical cancer patients(p<0.001).1.2 In the cervical cancer group,the single-type infection rate was 60.6%,32.3%in the multi-type infection rate,in the precancerous lesion group,the single-type infection rate was 48.4%,and 18.8%in the multi-type infection group.The difference between the two groups was statistically significant(p<0.001).Although the rate of single-type infection in the cervical cancer group was more than that in he cervical precancerous lesion group,the difference was not statistically significant.1.2.1 In HPV-positive patients,the majority of the two groups were mono-type infection both in cervical cancer and cervical precancerous lesions,of which the mono-type infection rate in the cervical precancerous lesions were 72.09%(31/43),and the single-type infection rates in the cervical cancer group were 65.22%(60/92).In the multi-type infection patients,the two groups were mainly double infection.The double infection rate of cervical precancerous lesions was 23.26%(10/43),and the double infection rate of cervical cancer was 25.0%(23/92).1.2.2 Analysis of different subtypes of HPV infection in cervical cancer and cervical precancerous lesions in multi-type infection.The most common top three were 16 subtypes(84.6%)and 18 subtypes(5.5%),52.Subtype(3.4%).1.2.3 Analysis of multi-type HPV infection in cervical cancer group and cervical precancerous lesion group,the most common top three are 16 subtype(42.2%),18 subtype(21.6%),and 58 subtype(1 1.8%).1.3 The 16-type infection rates in cervical cancer group and precancerous lesion group were 78.3%and 46.2%,respectively,while the non-16 infection rate in cervical cancer group and precancerous lesion group was 11.6%and 13.5%.There was a statistically significant difference in the HPV16 infection between the two groups.There was a statistically significant difference between the cervical cancer group and the cervical precancerous lesion group of non-16 type(P<0.001).Although the infection rate of type 16 was higher than that of non-16 type in the two groups,the difference was not statistically significant.2 Hardy-Weinberg equilibrium test results show that rs2853691(C>T),rs10069690(C>T),rs2853676(C>T),rs2853677(A>G),rs2075786(A>G),rs2736098(C>T),The rs2853690(A>G)and rs2736114(C>T)sites in the normal cervical,cervical precancerous and cervical cancer groups were p>0.005,consistent with the Hardy-Weinberg equilibrium.In the normal cervical group,rs2736122 locus p<0.05,the rest of the locus p>0.005,in line with the Hardy-Weinberg equilibrium,consider the precancerous lesion group and cervical cancer group at this locus and the remaining 8 SNP loci hTERT In the gene(p>0.005),the genotype distribution of the cervical cancer group,the precancerous lesion group and the normal cervical group were consistent with the Hardy-Weinberg equilibrium.3 In the haplotype construction,TGGCACACC was statistically different between the normal cervical group and the diseased cervical group(P<0.001).4 Linkage disequilibrium analysis showed that rs2853690(A>G)and rs2075786(A>G),rs2853690(A>G)and rs2736098(C>T),rs2736114(C>T)and rs2075786(A>G)There is a strong linkage disequilibrium relationship(D=0.978,0.985,0.881);the correlation between the other SNP loci is not obvious(D<0.8).5 Relationship between single nucleotide polymorphisms,HPV infection or not,single type infection and polytype infection,and infection of different subtypes of hTERT gene at 9 loci5.1 rs2736122In each stratified analysis,the frequency of AA genotype was 8.7%,the frequency of AG genotype was 88.4%,and the frequency of GG genotype was 2.9%in the normal cervix group.The frequency of AA genotype was 0,the frequency of AG genotype was 14.3%,the frequency of GG genotype was 85.7%;the frequency of AA genotype was 0 in cervical cancer group without HPV,the frequency of AG genotype was 14.3%,and the frequency of GG genotype was 85.7%.In the case of single-type infection and polymorphic infection,HPV 16 and non-16 infections,and no HPV infection,the difference in genotype frequency between the normal cervical group and the cervical precancerous lesion group and the cervical cancer group was statistically significant(p<0.001).In both single-type and multi-type infections,type 16 and non-16 infections,the A allele frequency of the normal cervical group was 52.9%,and the G allele frequency was 47.1%;the cervical precancerous lesion group had no AV in the HPV infection.The gene frequency was 7.1%,the G allele frequency was 92.9%,and the GG genotype frequency was 85.7%.In the cervical cancer group,there was no HPV infection,the A allele frequency was 7.1%,and the G allele frequency was 92.9%.Infection and polymorphism,HPV16 and non-16 infections,no HPV infection,normal cervical group and cervical precancerous lesions,cervical cancer group,allele frequency differences were statistically significant(p<0.001).There were no significant differences in alleles and genotypes between the subgroups with HPV infection,including single and multiple infections,HPV 16 and non-16 infections(p>0.05).5.2 rs2853677In the stratified analysis,in the subgroup with HPV infection or not,the rs2853677(A>G)locus in the normal cervical group had an AA genotype frequency of 29.9%,an AG genotype frequency of 49.3%,and GG genotype frequency of 20.9%.In the precancerous lesion group,the AA genotype frequency was 23.8%,the AG genotype frequency was 76.2%,and the GG genotype frequency was 0.In the cervical cancer group,the AA genotype frequency was 14.3%,and the AG genotype frequency was 28.6%.The genotype frequency was 57.1%.There was a statistically significant difference in genotype frequency between the three groups in the absence of HPV infection(P=0.01).In the HPV 16 and non-16 infection subgroups,the rs2853677(A>G)locus in the normal cervical group had an AA genotype frequency of 29.9%,an AG genotype frequency of 49.3%,and a GG genotype frequency of 20.9%;The frequency of AA genotype was 23.8%,the frequency of AG genotype was 76.2%,the frequency of GG genotype was 0;the frequency of AA genotype was 14.3%in cervical cancer group,the frequency of AG genotype was 28.6%,GG genotype The frequency was 57.1%,and the difference in genotype frequency between the three groups was statistically significant(P=0.008).There was no significant difference in allele frequencies at this locus(P>0.05).5.3 hTERT gene rs2853691,rs10069690,rs2853676,rs2075786,rs2736098,rs2853690 and rs2736114 7 SNP loci in three groups with HPV infection or not,haplotype and polytype infection,type 16 and non-type 16 infection genotype frequencies and alleles there was no statistically significant difference in gene frequency.Conclusion(s):1 The HPV16 subtype is the most common pathogenic subtype of cervical precancerous lesions and cervical cancer.The second most common is the 18 type.Other common types are the 58 and 52 subtypes.Whether the development of cervical cancer after HPV infection is mainly determined by the pathogenicity of the infected HPV subtype;single type infection and polytype infection are not directly related to the occurrence and development of cervical cancer..2 AG is mainly in normal cervical genotype in rs2736122,and A is the main allele,which may be a beneficial mutation,but it can not be biased by sampling error.3 The rs2853677(A>G)locus in patients without HPV infection,AA genotype for cervical cancer,is a protective genotype,which can avoid cervical cancer to some extent.The G allele may increase the incidence of cervical cancer.However,this site was not associated with HPV susceptibility,simple infection and multiple infections,type 16 infection,and non-type 16 infection.4 hTERT gene rs2853691(C>T)rs10069690(C>T),rs2853676(C>T),rs2075786(A>G),rs2736098(C>T),rs2853690(A>G)and rs2736114(C>T)7 Single nucleotide polymorphisms at SNP sites were no associated with HPV susceptibility to cervical precancerous lesions and cervical cancer patients,and no association between infection and multiple infections,16 infections,and non-16 infections.