Study On The Relationship Between HPV Infection, P53 Gene Condon 72 Polymorphism And Environment Factors With Oral Cancer And Its Prognosis

ObjectiveTo study the main influence factors of oral cancer; to explore the independent and interaction of p53 gene polymorphism and the occurrence of oral cancer in Fujian area; to find out the factors influencing the prognosis of oral cancer; to study the association between HPV infection and oral cancer; to predict the role of HPV infection in the prognosis of oropharyngeal squamous cell carcinoma.Methods1. A case-control study was applied, in which 364 patients of oral cancer confirmed by pathological diagnoses and 840 control subjects were matched in gender and age. Each subject were personally interviewed by using a standard questionnaire. Methods such as unconditional logistic regression model and crossover analysis were employed, to assess adjusted odds ratios(ORs) between influencing factors(tobacco smoking, alcohol drinking, tea) and the risk of oral cavity, and their corresponding 95% confidence intervals(CIs) respectively. The interaction effects of the main influence factors on oral cancer were also analysed.2. Biological samples of each participates were collected and their DNAs were extracted. p53 gene polymorphism was detected by polymerase chain reaction-restriction fragment length. Best genetic models were evaluated by MAX test. The association between p53 gene polymorphism and oral cancer, and the interaction effects of p53 gene polymorphism and environmental factors were analyzed by using Stata12.0. 3. By applying case-control study,75 cases with pathologic confirmation were recruited from the First Clinical Medical College and 75 control subjects matched to cases on age and gender from given communities were enrolled. Fresh specimens of oral cancer and mucosal tissues of control group were collected, and the genomic DNA was extracted from the two groups of samples, and HPV gene microarray method was also employed to detect 21 HPVs. Unconditional logistic regression model was performed to calculate odds ratios(ORs) and 95% confidence intervals(CIs) of HPV16/18 infection in oral cancer. 4. According to prospective clinical follow-up, oral cancer patients were followed up prospectively every 6 months from the time of enrollment by oral cancer patients or family contacts. The clinical and follow-up data of 705 patients were gathered to explore the prognosis factors of oral cancer. 5. Meta analysis was conducted to collect data, and estimate the quality of literature. Stata12.0 was employed to evaluate the heterogeneity and publication bias. Stata 12.0 was also used to calculating the Overall HR and 95% CI for the evaluation of HPV infection effects on the prognosis of oropharyngeal squamous cell carcinoma.Results1.Multivariate unconditional logistic regression analysis indicated that cigarette smoking above 50 packs/year, smoking within the first 30 minutes after getting up, secondhand smoking before age 18, average daily alcohol consumptions no less than 60 g, family history of cancer, body mass index less than 18.5kg/m2, bad prosthesis and dental ulcer were risk factors of oral cancer,body mass index above 24kg/m2, drinking warm tea, regularly taking supplements, regularly taking vitamin supplements, green vegetables over once a day, seafood and fish no less than once a day, other vegetables no less than once a day, taking fruits at least 1 time a day, regular oral health examination at least 5 years per time were the protective factors of oral cancer. Synergic effect between tobacco smoking and alcohol drinking in the risk of oral cancer was 2.308(1.109, 4.803). 2. Compared with Arg/Arg genotype, p53 gene with Pro/Pro genotype was associated with higer risk of oral cancer(OR=1.837); The interaction of p53 gene with Pro/Pro genotype and alcohol drinking was OR 13. 616(95%CI :4.731~39.183).3. HPV16/18 infection obviously increase the risk of oral cancer with OR 12.457(95%CI: 1.325~117.117); HPV infection was correlated with age, gender, education level, smoking and drinking(P<0.05); No obvious association between HPV infection and p53 gene polymorphisms was identified(P>0.05). 4. Gender,education level, family history of cancer, alcohol drinking, T stage, M stage, histological grade, tumor size, tumor recurrence, and diagnosis of lymph node metastasis for the first time, surgical treatment, oral hygiene were prognostic factors affecting the overall survival of oral cancer(P<0.05); education level, family history of cancer, tumor size, T stage, histological grade, and diagnosis of lymph node metastasis for the first time, and surgical treatment were factors affecting the disease free survival of oral cancer(P<0.05). 5. Patients with oropharyngeal squamous cell carcinoma with HPV-positive indicated a lower risk of death(meta HR:0.33,95%CI: 0.29~0.38), and a lower risk of recurrence of cancer(meta HR: 0.35,95%CI: 0.29~0.40).Conclusions1. Cigarette smoking and alcohol drinking are the main risk factors of oral cancer and there is synergic effect between the two factors in the occurence of oral cancer; more intake of fruit and vegetables can reduce the risk of oral cancer.2. p53 gene with Pro/Pro genotype may be related to susceptibility of oral cancer in Fujian area. 3. HPV16/18 infection may be the risk factors of oral cancer and HPV infection is related to age, gender, education level, smoking and drinking in Fujian Area;There is no obvious association between HPV infection and p53 gene polymorphisms. 4. There is association between education level, family history of cancer, tumor size, T stage, histological grade, and diagnosis of lymph node metastasis for the first time, surgical treatment and the prognosis of oral cancer. 5. HPV positive favored the prediction of the prognosis of oropharyngeal squamous cell carcinoma.