p53基因第72位密码子多态性与宫颈癌及HPV-16、18E6之间关系的研究

p53 Codon 72 Polymorphism in Cervical Cancers and Its Correlation with HPV16,18E6

目的探讨宫颈癌及其癌前病变中p53基因第72位密码子多态性的表达及其与HPV16、18E6表达之间的关系，以了解p58基因第72位密码子多态性是否可以作为预测宫颈癌发生的一项高危因子。方法以PCR法检测81例宫颈鳞癌（高分化13例、中分化24例、低分化44例；Ⅰb期24例、Ⅱa期15例、Ⅱb期37例、Ⅲa期5例）、18例宫颈腺癌、88例宫颈上皮内瘤样病变（CINⅡ30例、CINⅢ58例）及60例正常宫颈组织中p53基因第72位密码子多态性及HPV16、18E6的表达。结果p53Arg纯合子、p53Arg／Pro杂合子及p53Pro纯合子在宫颈鳞癌、腺癌和CIN（Ⅱ～Ⅲ）中分别占58．02％、30．86％、11．12％；55．55％、27．78％、16．67％I59．09％、21．59％、19．32％。各组中p53Arg纯合子明显高于p53Arg／Pro杂合子及p53Pro纯合子，且差异有统计学意义（P〈0．05IP〈0．01）。正常宫颈组织中p53Arg纯合子、p53Arg／Pro杂合子及p53Pro纯合子分别为23．33％、40．OO％、36．67％，三者间无统计学意义（P〉0．05）。宫颈癌组（鳞癌及腺癌）、CIN（Ⅰ～Ⅱ）组中p53Arg纯合子均高于正常对照组中p53Arg纯合子，且差异有统计学意义（P〈0．05）；宫颈鳞癌中HPVl6、18E6（＋）亚组中p53Arg纯合子显著高于HPV16、18E6（-）亚组及HPVl6、18E6（＋）正常对照组亚组（P〈0．05，P〈0．01）。各组中p53Arg纯合子均高于p53Pro纯合子（P〈0．05）；p53Arg纯合子及等位基因均未随宫颈癌临床分期及分化程度而变化，与宫颈癌前病变程度亦无关系。结论p53Arg纯合子可作为预测宫颈癌及其癌前病变的一项高危因子，与高危型HPVE6同时检测可提示宫颈病变的发展趋势；p53Arg纯合子与宫颈癌临床分期及分化程度无明显相关性。

Objectives To examine p53 codon 72 polymorphism＇in cervical cancers and its correlation with HPV16/18 E6. Methods Cervical specimens were taken from 81 patients with cervical squamous cancer, 18 patients with cervical adenocarcinoma, 88 patients with CIN Ⅱ - Ⅲ and 60 patients without cancers. PCR was used to examine the p53 genotypes and the expression of HPV16 and 18 E6. Results The frequencies of p53 Arg homozygosity in cervical squamous cancer, cervical adenocarcinoma and CIN （ Ⅱ - Ⅲ ） were 58. 02%, 55.55% and 59. 09% respectively, greater than those of p53 Arg/Pro heterozygosity （30. 86%, 27.78%, 21.59%） and those of p53 Pro homozygosity （11.12%, 16.67%, 19.32%）. The normal cervical samples also showed less frequency of p53 Arg homozygosity （23. 33%） than cervical squamous cancer. There were no significant differences in the frequencies of p53 Arg homozygosity, p53 Arg/Pro heterozygosity and p53 Pro homozygosity （23.33 % ,40. 00% and 36.67% respectively）. The frequency of HPV16,18 E6-positive in cervical cancer and CIN was much higher than that in control group （81.84%, 50. 00% and 53.41%） for the normal cervical samples. The expression of HPV16 and 18 E6 in cervical squamous cancers was more frequent than in CIN. The frequency of p53 Arg homozygosity in HRHPV E6-positive cervical squamous cancers （64. 06%） was greater than in HRHPV E6- negative cervical squamous cancers （35.29%） and in HRHPV E6-positive normal samples （33.33%）. The p53 codon 72 polymorphism showed no differences in samples with different FIGO staging and grades. Conclusion p53 Arg homozygosity could serve as a risk indicator for the tumorigenesis of cervix. In combination with HRHPV E6, it might be able to predict the progression of cervical lesions, p53 codon 72 polymorphism is not associated with FIGO staging and grades of cervical cancers.