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Interaction of Folic Acid, DNA Methyltransferases 1 and FHIT Gene Methylation in Cervical Lesions

Author: HuoXiaoXu
Tutor: WangJinTao
School: Shanxi Medical
Course: Epidemiology and Biostatistics,
Keywords: Cervical lesions Folic acid Human papillomavirus type 16 FHIT gene DNA methyltransferase 1
CLC: R737.33
Type: Master's thesis
Year: 2010
Downloads: 127
Quote: 2
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Abstract


The purpose of cervical cancer is one of the common female malignancy has clear human papilloma virus (human papillomavirus, HPV) infection is a major cause of cervical cancer occur, but not the only factor. Recent studies show that folic acid deficiency can increase cervical cancer risk. Folic acid is one of the body's essential micronutrients, as a major donor of the body a carbon units, involved in DNA methylation process is closely related with the development of tumor. With the deepening of the epigenetics research has found that the incidence of cervical cancer, the presence of DNA methylation level and pattern of development disorders. In view of the lack of folic acid and DNA methylation in the process of cervical lesions have an essential role, and inextricable intrinsic link between folic acid and DNA methylation, suggesting that folic acid may be through regulation of methylation as collaborative factors play a role in the process of cervical lesions. In this study, the women of different cervical lesions as the research object, play an important role in defining premise of HPV infection and the body's folate levels detected in DNA methylation DNMT1 protein expression changes and tumor suppressor genes FHIT target gene, folic acid, DNMT1 protein expression, FHIT gene CpG island methylation and cervical cancer to assess the relationship between the development of cervical lesions interactions to provide new ideas for the prevention and control of cervical cancer. The method based on population studies, case-control study group, select from June 2008 to August 2009 in Shanxi Tumor Hospital pathologically-confirmed cervical squamous cell carcinoma incidence of 100 cases as case group select the same period in the Second Hospital of Shanxi Medical gynecological treatment of cervical intraepithelial neoplasia (CIN) in patients like change of 101 cases and 109 cases of chronic cervicitis, as the case group and control group, respectively. Cases and controls need to exclude nutritional megaloblastic anemia, hemolytic disease, leukemia, enteritis, liver disease, other cancer patients, as well as three months of the B family vitamins user. Collected through questionnaires research object demographic characteristics, reproductive factors, and other related information under the principle of informed consent, the acquisition object of study fasting blood biopsy and surgery or colposcopy cervical tissue. By radioimmunoassay (RIA) serum folic acid; HPV16 infection detected by PCR amplification; Western Blotting method to detect the expression level of DNMT1 protein; methylation-specific PCR (MSP) was used to detect the FHIT gene CpG island The methylation status. Use the SPSS16.0 software analysis data, the normal distribution data using t-test and variance analysis, the skewed distribution of data using the Wilcoxon test and the Kruskal-Wallis test, classification data using χ2 test, χ2 test trends and related factors were analyzed by a single factor analysis and multivariate unconditional logistic regression analysis, interaction analysis fork Health. Results (1) of HPV16 infection rate in the cervical cancer group (61.0%) and CIN group (38.6%) were significantly higher than that of the control group (20.2%), the difference was statistically significant (χ 2 = 36.29, P = 0.000; χ2 = 8.64, P = 0.003). (2) serum folate levels in the cervical cancer group (1.86 ± 2.14ng/ml) was significantly lower than the control group (3.19 ± 2.50ng/ml) but in the CIN group (2.60 ± 2.46 ng / ml) and the control group was not significant difference; With the decline in the level of serum folate, the risk of cervical cancer is gradually increasing (χ2 trend = 14.842, P1 = 0.000). (3) expressions of DNMT1 protein expression levels in the cervical cancer group (2.93 ± 0.36) and CIN group (1.87 ± 0.33) was significantly higher than that in the control group (0.89 ± 0.30), differences were statistically significant; (4) FHIT gene CpG island methylation rate of cervical cancer group (39.0%) was significantly higher than that of the control group (2.8%) (χ 2 = 42.67, P = 0.00), but in the CIN group (3.0%), and no significant difference between the control group (χ2 = 0.00, P = 1.00). With the progress of cervical lesions of FHIT gene CpG island methylation rate gradually increased (χ2 trend = 53.56, P = 0.000); qualitative analysis (5) of the interaction of biological serum folate DNMT1 protein expression: In cervical cancer and CIN, the interaction between these two factors there are positive sum. (6) in cervical cancer between serum folate and FHIT gene CpG island methylation between expressions of DNMT1 protein expression of the FHIT gene methylation positive sum interaction, but were not found them in CIN Positive additive effect. (7) in cervical cancer, HPV16, serum folate, FHIT gene CpG island methylation, serum folate * DNMT1 protein expression, education level, age of first sex and pregnancies as a major factor in the regression model; in CIN HPV16 infection, the age of first sex and pregnancies, three factors were introduced into the regression equation. Conclusions (1) low serum folate levels are risk factors for cervical cancer, expressions of DNMT1 protein overexpression has an important role in the occurrence of cervical cancer and CIN both synergies that may exist in the incidence of cervical cancer, but the incidence of CIN not found in the synergy between the two. (2) of FHIT gene CpG island methylation increase cervical cancer occur dangerous. (3) HPV16 infection first sex younger pregnancies cervical cancer and CIN common risk factors, the cultural high degree of cervical cancer has a protective significance.

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CLC: > Medicine, health > Oncology > Genitourinary tumors > Female genital tumors > Uterine tumors
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