Folic Acid And Fhit Gene Methylation In Cervical Lesions

ObjectiveThe cervix cancer is the second malignant tumor in woman.High-risk HPV16 infection is major and non unique reason of cervix cancer.Folic acid being donor of one carbon unit that participate DNA methylation is closely related to cervix cancer.In the recently years the datas show hypermethylation of FHIT gene CpG island is correlated with cervix cancer and HPV16 is integrated into the fragile sites of FHIT gene,that possibly have interaction,but we don't have seen correlated report.The study is premise of HPV16 infection to discuss effect of folic acid and FHIT gene CpG island methylation in cervical lesions and their possible interaction.MethodsA hospital-based case-control study was conducted in The Second Clinical Hospital of Shanxi Medical University from Jane 2008 to December,the study included pathology definite,nulli-radiotherapy,nulli-chemotherapy and new cervical lesions cases 108:LSIL 40 cases,HSIL 49 cases and SCC 19 cases and 108 controls of chronic cervicitis from the same time without blood relationship with the cases with the same age,ethnic and place of residence.All subjects were informed consent for research.Serum folic acid in blood samples was measured using RIA and HPV16 from surgical biopsy was gained by PCR and FHIT gene CpG island methylation was detected by MSP for all the subjects.Statistical analysis was used by the SPSS13.0,T-test was used by quantitative data in normal distribution;Kruskal-wallis and Nemenyi were used by the skewed distribution;χ2 test andχ2 trend test were used by qualitative data;Crossover analysis was used by interaction.Results1. Association between serum folic acid, HPV16 and cervical lesions(1) Serum folic acid and cervical lesionsSerum folic acid level in HISL(1.69±0.42ng/ml) and SCC(1.36±1.664ng/ml)is lower than that in control (3.09±1.98ng/ml);Using Kruskal-wallis and Nemenyi testing,there is difference between HSIL,SCC and control in serum folic acid level(H=58.044,P=0.000;H=70.479, P=0.000).(2) HPV16 and cervical lesionsHPV16 infection rate in HSIL(42.9%) and SCC(56.1%) is higher than that in control (29.6%),there is difference between HSIL, SCC and control(χ2=2.64,P=0.033;χ2=8.02,P=0.005).(3) Serum folic acid and HPV16 were associated with cervical lesionsThe results of Crossover analysis show that the risk of folic acid deficiency and HPV16 infection in SCC(OR=31.31) is higher than that when HPV16 infection(OR=1.95)and folic acid deficiency (OR=5.69).2. Serum folic acid, FHIT gene CPG island methylation and cervical lesions(1) Serum folic acid and FHIT gene CPG island hypermethylationRate of FHIT gene CPG island hypemethylation(31.7%) in low serum folic acid(<2.30ng/ml) is higher than that(2.2%) in high serum folic acid(≥2.31ng/ml),there is difference (χ2=29.22,P=0.000), the odds ratio is 20.47,95%CI:4.80-87.32.(2) FHIT gene CPG island methylation and cervical lesionsRate of FHIT gene CPG island methylation in LSIL(12.5%),HSIL(44.9%) and SCC(63.2%) is higher than the control(2.9%),the odds ratio is 5.0,8.52 and 60.00;95%CI is (1.14-22.00, 1.14-22.00 and 7.94-102.39).(3) Serum folic acid and FHIT gene CPG island methylation were associated with cervical lesionsThe results of Crossover analysis show that risk of serum folic acid deficiency and FHIT gene CPG island hypermethylation in SCC(OR=8.33) is higher than that when serum folic acid deficiency (OR=1.53)and FHIT gene CPG island hypermethylation(OR=1.39).(4) HPV16 and FHIT gene CPG island hypermethylation were associated with cervical lesionsThe results of Crossover analysis show that the risk of HPV16 infection and FHIT gene CPG island hypermethylation in SCC (OR=63.13) is higher than that when FHIT gene CPG island hypermethylation (OR=18.94) and HPV16 infection (OR=9.47).The risk of cervical lesions when FHITgene CPG island hpermethylation is higher than that HPV16 infection.Conclusions1. Serum folic acid deficiency and HPV16 infection was associated with the development of cervical lesions, they possibly have interaction in the development of cervical lesions.2. Serum folic acid deficiency was related to FHIT gene CPG island hypermethylation,FHIT gene CPG island hypermethylation can increase the risk of cervical lesions.3. Serum folic acid deficiency and FHITgene CPG island hypermethylation in cervical lesions may have interaction;HPV16 infection and FHIT gene CPG island hypermethylation in cervical lesions may have interaction.The risk of cervical lesions when FHIT gene CPG island hypermethylation may be higher than that HPV16 infection.