Oliveira S, Sousa H, Santos A M, Pinto D, Pinto-Correia A L, Fontoura D, Moutinho J, Medeiros R
Molecular Oncology Group and Virology Service, Portuguese Institute of Oncology of Porto, Rua Dr. António Bernardino Almeida, Porto, Portugal.
J Med Virol. 2008 Mar;80(3):424-9. doi: 10.1002/jmv.21103.
The interaction between the E6 protein of the high-risk human papillomaviruses (HPVs) with p53 seems to be crucial in cervical carcinogenesis. The presence of Arg/Arg genotype at codon 72 of TP53 gene was characterized as a risk factor in development of cervical cancer. However, the role of this polymorphism remains controversial and some authors suggested that the origin of DNA (blood or exfoliated cervical cells) might influence these results. This study analyzed the effect of the p53 codon 72 polymorphism (R72P) in exfoliated cervical cells of women from the northern region of Portugal using two methodologies: allele-specific polymerase chain reaction and real-time polymerase chain reaction. We studied 700 cervical exfoliated cells which showed: 334 cases from women without cervical cancer or cervical lesion (N), 114 low-grade squamous intraepithelial lesions (LSIL), 107 high-grade squamous intraepithelial lesions (HSIL), 20 invasive cervical cancers (ICC) and 125 atypical squamous cells of unknown significance (ASCUS). No statistically significant differences between cases and controls were found, regarding the influence of the R72P polymorphism with cytological classification, high risk-HPV infection and HPV16 presence (P = 0.336, P = 0.945, and P = 0.964, respectively). Also, the influence of this polymorphism in the median age of onset for LSIL, HSIL, and ICC was not statistically significant (P = 0.674, P = 0.810, and P = 0.928, respectively). Therefore, the hypothesis that women with Arg/Arg genotype have an increased risk of developing cervical cancer failed to be proven in this study. Moreover, our study reveals that results using exfoliated cervical cells are reliable as compared with studies on blood.
高危型人乳头瘤病毒（HPV）的E6蛋白与p53之间的相互作用在宫颈癌发生过程中似乎至关重要。TP53基因第72密码子处的精氨酸/精氨酸（Arg/Arg）基因型被确定为宫颈癌发生发展的一个危险因素。然而，这种多态性的作用仍存在争议，一些作者认为DNA的来源（血液或宫颈脱落细胞）可能会影响这些结果。本研究采用两种方法分析了葡萄牙北部地区女性宫颈脱落细胞中p53第72密码子多态性（R72P）的影响：等位基因特异性聚合酶链反应和实时聚合酶链反应。我们研究了700例宫颈脱落细胞，其中包括：334例无宫颈癌或宫颈病变的女性（N）、114例低级别鳞状上皮内病变（LSIL）、107例高级别鳞状上皮内病变（HSIL）、20例浸润性宫颈癌（ICC）以及125例意义不明确的非典型鳞状细胞（ASCUS）。就R72P多态性对细胞学分类、高危型HPV感染及HPV16存在情况的影响而言，病例组与对照组之间未发现统计学上的显著差异（P值分别为0.336、0.945和0.964）。此外，这种多态性对LSIL、HSIL和ICC发病年龄中位数的影响也无统计学意义（P值分别为0.674、0.810和0.928）。因此，本研究未能证实Arg/Arg基因型女性患宫颈癌风险增加这一假说。此外，我们的研究表明，与血液研究相比，使用宫颈脱落细胞得出的结果是可靠的。
