Folic Acid, The Role Of Fhit Gene Methylation In Cervical Lesions

ObjectiveThe cervix cancer is the second malignant tumor in woman. It is second to breast cancer as the most common malignancies in incidence. High-risk HPV16 infection is major and non unique reason of cervix cancer. The study is premise of HPV16 infection to discuss effect of folic acid and FHIT gene 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 December 2008 to February2009, the study included pathology definite,nulli-radiotherapy,nulli-chemotherapy and new squamous carcinoma of the cervix cases 80, CIN 80 cases (CINⅠ22cases, CINⅡ30cases, CINⅢ28cases) and 82 controls of hysteromyoma 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. All participants required Shanxi resident, Han people, and people who had cerebrovascular disease, haemolyticus disease, digestive system disease, VitB supplement within 3 months lately and other dysplasias were considered ineligible for study. A standardized questionnaire was used to collect the information of intake folic acid, Serum folic acid in blood samples was measured using RIA, FHIT gene CpG island methylation was detected by MSP for all the subjects. Statistical analysis was conducted by SPSS 13.0 software.Results1. Association between folic acid and cervical lesions(1) Dietary folate and cervical lesionsDietary folate intake in CIN (5.00±0.41μd/kcal) and cervical cancer group (4.87±0.32μd/kcal) is lower than that in control (5.14±0.35μd/kcal), with a statistically significant difference.(2) Serum folic acid and cervical lesionsSerum folic acid level in control group (3.25±1.89) ng/ml and CIN group (2.79±1.33) ng/ml is higher than that in cervical cancer group(1.96±1.07)ng/ml; Serum folic acid level in control group (3.25±1.89) ng/ml is higher than that in CIN group (2.79±1.33) ng/ml. There is difference between control group, CIN group and cervical cancer group (F=864.53, P=0.000).2. Association between FHIT gene CpG island methylation and cervical lesionsRate of FHIT gene CpG island methylation in cervical cancer group (35.0%) is significant higher than that in control group (3.7%), with a statistically significant difference (χ2=25.71, P=0.00)。But there is not a statistically significant difference between CIN group (3.8%) and control group (χ2=0.00, P=1.00).3. Serum folic acid, FHIT gene CpG island methylation and cervical lesions(1) Serum folic acid and FHIT gene CpG island methylationRate of FHIT gene CpG island hypemethylation(18.7%) in low serum folic acid(< 2.30ng/ml) is higher than that(10.4%) in high serum folic acid(≥2.31ng/ml),there is difference (χ2=8.22, P=0.00), the odds ratio is 5.47,95%CI (2.80-57.32).(2) 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 cervical cancer is higher than that when serum folic acid deficiency and FHIT gene CpG island hypermethylation. The risk of serum folic acid deficiency and FHIT gene CpG island hypermethylation in cervical cancer is 29.33 times than normal.Conclusions1. Serum folic acid deficiency was associated with the development of cervical lesions.2. FHIT gene CpG island hypermethylation can increase the risk of cervical lesions.3. Serum folic acid deficiency was related to FHIT gene CpG island hypermethylation,they may have interaction in cervical lesions.