Study On Correlation Between P53Arg72Pro Polymorphisms And Carcinogenic Mechanism In HPV-associated Cervical Carcinoma

Objective: To investigate the biological functions which include cellular proliferation,transcriptional activation and promoting cellular apoptosis of the p53Arg72Pro different genotypes, and to explain the relationship between the p53Arg72Pro polymorphisms and carcinogenic mechanism in HPV-associated cervical carcinoma with the distribution of p53Arg72Pro polymorphism and infection of HPV16. Methods: PCR and PCR-RFLP were performed to detect the p53Arg72 Pro genotypes distribution in 152 cases of cervical carcinoma and 100 cases of normal cervical tissue in Uigur women, 120 cases of cervical carcinoma and 122 cases of normal cervical tissue in Han women in Xinjiang. PCR for HPV16DNA, Immunohistochemistry for the expression of P53, P21, Bax, Ki-67 protein and apoptotic index were used to detect 210 cases of carcinoma and 95 cases of normal.Results: (1) The frequency of Arg/Arg was higher in Uigur cervical carcinoma and the frequency of Pro/Pro was higher in Han cervical carcinoma on the distribution of p53Arg72Pro polymorphism in cervical carcinoma and normal, and there were significant differences (P<0.05); (2) The HPV16DNA infection rate in cervical carcinoma (70.5%) was higher than normal, and there were significant differences (P<0.05); (3) The expression of P53, P21, Bax, Ki-67protein and apoptosis index in cervical carcinoma were higher than normal, and there were significant differences (P<0.05); (4) In HPV positive cervical carcinoma, the weakly positive and negative rate of P53 protein was higher than the strong positive rate, there were no significant differences, and the negative rate of P53 Arg protein was higher than P53 Pro protein, the difference was significant (P<0.05); (5) In HPV positive cervical carcinoma, the weakly positive and negative rate of P21 protein was higher than the strong positive rate, there were no significant differences, the negative rate of P21 protein in p53 Pro genotype was higher than p53 Arg genotype, there were no significant differences, the PI of the weakly positive and negative groups were higher than the strong positive groups, and the differences were significant (P<0.05), In the weakly positive and negative group the PI of p53 Pro genotype was higher p53 Arg genotype, and there were significant differences (P<0.05); (6) In HPV positive cervical carcinoma, the weakly positive and negative rate of Bax protein was higher than the strong positive rate, there were no significant differences, the negative rate of Bax protein of p53 Pro genotype was higher than p53 Arg genotype, the differences was significant (P<0.05), the AI of the weakly positive and negative groups were lower than the strong positive groups, and the differences were significant (P<0.05), In the weakly positive and negative group the AI of p53 Pro genotype and p53 Arg genotype were decreased, but there were no significant differences.Conclusions: (1) p53 Arg/Arg may be a susceptible factor for cervical carcinoma in Uigur women, and p53 Pro/Pro may be a susceptible factor for cervical carcinoma in Han women; (2) P53 protein may be degraded completely or partly by HPVE6 protein, by which P53 Arg protein may be easier to be degraded; (3) When P53 Arg protein, P53 Pro protein are degraded, there are differences in the degree of inhibiting cellular proliferation and promoting cellular apoptosis and they may have different carcinogenic mechanisms in cervical carcinoma, and the function of transcripting p21, Bax gene and blocking cell cycle of P53 Pro protein would be decreased significantly.