Folate Metabolic Enzymes In The Mthfr, Ms Gene Polymorphism And Cervical Cancer Susceptibility

Objective:Hereditary susceptibility and gene polymorphism play a significant role in the development of cervical cancer. The impact of polymorphism in folate metabolizing enzyme on cervical cancer has not been cleared.In this work,we have assessed the role of MTHFR and MS polymorphisms in cervical cancer development and its interaction with HPV16 and other environment factors.Methods:A hospital-based case-control study was conducted. Patients who had taken colposcope and pathological diagnosis at Shan xi Medicine University Second Hospital and Shanxi Tumor Hospital during March to October,2008 and January, 2005 to June, 2005 were recruited. 56 pairs of cervical cancer to CIN in 1:1 and 78 pairs of cervical cancer to cervicitis control in 1:1 were sampled in random from eligible Patients(120 with cervical carcinoma and 78 with CIN)and 177 eligible control. All cases and controls were investigated directly by medical staff with the same cervical cancer risk factors questionnaires.Cervix uterine tissues sample were collected from all participants. HPV 16 infection status and virus-oncogene E2 deletion were determined by multi-PCR method. MTHFR and MS gene polymorphism were determined by PCR-RFLP method.Single factor analysis has been taken by chi-square test and multiple non-conditional logistica regression.Multi-Colinearity and hidden extraction variables analysis has been taken by factorial analysis.Potential interactions were explored by ading interaction itmes to the multi-variate logistic regression.Results: The result of single factor analysis showed that HPV 16 infection,MTHFR and MS gene polymorphism,virus-oncogene E2 deletion,habitation,family size,number of children,bath frequency,washing pudendum after intercourse,age at first pregnancy, age at begining to long term birth control, times of childbirth,menstrual circal and menorrhea period were all associated with cervical cancer,among which, HPV 16 infection,virus-oncogene E2 deletion,family size,number of children,times of childbirth is precancerous lesion risk factors,and HPV 16 infection,MTHFR and MS gene polymorphism,virus-oncogene E2 deletion,habitation,family size,number of children,bath frequency,times of childbirth,menstrual circal and menorrhea period is risk factors of the stage from precancerous lesion to cancer.How ever,even other factors adjusted in single factor analysis,the relationship between MTHFR and cervical cancer is hard to charge which is caused by the big fluctuation in OR, ORMTHFR=3.396 (95% confidence interval 0.653～17.667,P=0.014). Environment factors with high multi-colinearity analysed by factorial analysis were orthogonal rotation changed into four hidden extraction variables,among which FAC1 mainly reflects family size,number of children and times of childbirth, FAC2 mainly reflects menstrual circal and menorrhea period, FAC3 mainly reflects habitation and bath frequency,while FAC4 mainly reflects age at first pregnancy and age at begining to long term birth control. After MTHFR and MS gene polymorphism,HPV 16 infection, virus-oncogene E2 deletion,hidden extraction variables and potential interactions were taken analysis by the interaction analysis and multi-variate logistic regression,we found out that MTHFR,HPV 16 infection and FAC1 were all associated with cervical cancer,the relationship between MTHFR and cervical cancer is significant(ORMTHFR=2.829,95%CI:1.020～7.846, P=0.046),but that of MS was excluded(χ2=1.104,P=0.293). HPV 16 infection and virus-oncogene E2 deletion were related with precancerous lesion,excluded MTHFR and MS(P value is 0.541and 0.583).Only the interaction between MTHFR and HPV 16 infection has the significant relationship with the stage from precancerous lesion to cancer(OR=1.923,95%CI:1.247～2.965,P=0.003).No interaction was found by cross table interaction analysis.Conclusions: MTHFR mutation is a risk factor in cervical cancer hereditary susceptibility.Probably, MTHFR has a interaction with HPV 16 infection to worsen the stage from precancerous lesion to cancer together,which need more investigations.MS polymorphisms is not found to play any role in the development of cervical cancer.