| Background and ObjectiveCervical cancer is the fourth-largest malignant tumor among women in the world.In recent years,the incidence of cervical cancer is still on the rise.High-risk HPV infection is the main cause of cervical cancer.However,there are large individual differences in viral infections and whether they cause cervical lesions after infection,and they are genetically susceptible.The APOBEC3B gene belongs to the family of apolipoprotein B m RNA-edited catalytic peptide-like 3(APOBEC3)family,which plays a role in the body against retroviruses(including HPV virus).And the APOBEC3B gene will also deaminate the host cell gene cytosine to cause C-T mutations,leading to the occurrence of cancer.GWAS has found that the29.5 kb coding sequence is deleted between exon 5 of APOBEC3A and exon 8 of APOBEC3B,resulting in the complete removal of the coding region of APOBEC3B and the formation of a new fusion gene APOBEC3A?B.Recent studies have found that this fusion gene will increase the susceptibility of various cancers.Therefore,this study mainly analyzed the association between APOBEC3B gene deletion and cervical precancerous lesions and cervical cancer risk Methods1.A case-control study design with 664 subjects was performed,including 96 cases of cervical cancer,284 cases of cervical precancerous lesions,and 284 healthy controls.The subjects were investigated with epidemiological questionnaires,and cervical exfoliated cells and 5 ml of peripheral venous blood were collected for related tests.2.Extract RNA and DNA from peripheral blood,apply real-time qualitative PCR(q PCR)method to genotyping all participants,and use real-time fluorescence quantitative PCR(RT-q PCR)method to determine APOBEC3A and APOBEC3B m RNA expression.3.SPSS 24.0 and Graph Pad Prism 7.0 software were used for data analysis and picture production.Data analysis methods include ANOVA analysis of variance,chi-square test,logistic regression analysis,and the generalized multi-factor dimensionality reduction method(GMDR)was used to analyze the interaction between genes and the environment.Results1.Univariate analysis found that there were statistical differences in age,BMI,age at menarche,age at first sex,number of sexual lives,number of pregnancies,number of miscarriages,and HPV infection among the three groups(P<0.05).There was no statistical difference in pregnancy age(P>0.05).2.After adjusting the number of sexual behaviors,the number of pregnancy,and HPV infection,the ratio of ID genotype and ID+DD genotype in the cervical precancerous lesion group to II was lower than that of the control group(ORID=0.66,95%CIID=0.44-0.99;ORID+DD=0.66,95%CIID+DD=0.45-0.96),and APOBEC3A?B genotype is not related to the occurrence of cervical cancer.The distribution of genotypes in the control group was in line with Harwinberg equilibrium(P>0.05).3.The correlation analysis between APOBEC3A?B genotype and cervical precancerous lesions shows that:in the comparison of II and DD genotypes,age>42 years old,BMI is 24?27.9 kg/m~2,age at menarche?15 years,age at first sex?23 years old,the first pregnancy age?24 years old,the number of pregnancy?2 times are statistically different(P<0.05);In the comparison of II and ID genotypes,menarche age?15 years old,first sex age?23 years old Statistical difference(P<0.05).The correlation analysis between APOBEC3A?B genotype and cervical cancer showed that the difference was not statistically significant(P>0.05).4.Interaction(1)In cervical precancerous lesions,the second-order interaction model(Genotype/HPV)was statistically significant(P<0.0010),with TBA of 72.51%and CVC of 10/10,suggesting the gene-environment of APOBEC3A?B Interactions play a role in cervical precancerous lesions.(2)In cervical cancer,the second-order interaction model(Primary sex age*Number of live births)was statistically significant(P<0.001),with TBA of 72.92%and CVC of 10/10,suggesting the gene-environment of APOBEC3A?B Interaction does not play a role in cervical cancer.5.Results of APOBEC3A and APOBEC3B m RNA expression in cervical cancer,cervical precancerous lesions and normal control group.The expression of APOBEC3A m RNA in cervical cancer is higher than that of cervical precancerous lesions and normal control group,which is statistically different(P<0.0001).The expression of APOBEC3B m RNA in cervical cancer and cervical precancerous lesions is higher than that of normal control group.There were statistical differences(P<0.0001);in cervical cancer,the expression of APOBEC3A m RNA was higher than that of APOBEC3B m RNA,and there was a statistical difference(P<0.0001).5.The expression level of A3A m RNA in the cervical cancer group was higher than that in the precancerous lesion group and the control group,and the difference was statistically significant(P<0.0001).The expression level of A3B m RNA in cervical cancer group and precancerous lesion group was higher than that in the control group,and the difference was statistically significant(P<0.0001).In cervical cancer,the expression of A3A m RNA was higher than that of A3B m RNA,and the difference was statistically significant(P<0.0001).6.The expression level of A3A m RNA in each genotype was higher in the cervical cancer group than in the precancerous lesion group and the control group,and the difference was statistically significant(P<0.001).Compare the expression of A3A m RNA in A3B+/+,A3B+/-and A3B-/-in the cervical cancer group,precancerous lesion group and control group,respectively.In the cervical cancer group,the ratio of A3B-/-expression to A3B+/+and A3B+/-The expression of A3B is high,and the difference is statistically significant(P<0.0001);A3B+/+expression is higher than A3B+/-(P<0.05),and in the A3B-/-genotype,A3B m RNA is basically not expressed.In the A3B+/+and A3B+/-genotypes,the expression of A3B in the cervical cancer group was higher than that in the precancerous lesion group and the control group,with statistical differences(P<0.001).7.In HPV+and A3B+/+,the expression of A3A m RNA in the precancerous lesion group was not significantly different from the control group(P>0.05);in HPV+and A3B-/-or A3B+/-,A3A m RNA The expression in the precancerous lesion group was not statistically different from that in the control group(P>0.05).Also in HPV+and A3B+/+,the expression of A3B m RNA in the precancerous lesion group was not statistically different from the control group(P>0.05).8.Correlation analysis of the m RNA expression of APOBEC3A and APOBEC3B in cervical cancer and cervical precancerous lesions,the difference was not statistically significant(P>0.05).9.Kaplan-Meier curve results show that cervical cancer patients with low A3B expression have a better prognosis than cervical cancer patients with high A3B expression(P=0.000223);A3A expression has nothing to do with the prognosis of cervical cancer(P=0.106).ConclusionsThe one-copy deletion and dominant model in APOBEC3B deletion polymorphism were protective factors for cervical precancerous lesions,and the lower expression of APOBEC3B is related to the overall survival rate of cervical cancer patients. |
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