卵巢癌患者中p53基因内含子2多态性的评估。来自丹麦“Malova”卵巢癌研究。

Evaluation of a polymorphism in intron 2 of the p53 gene in ovarian cancer patients. From the Danish "Malova" Ovarian Cancer Study.

作者信息

Høgdall Estrid V, Kjaer Susanne K, Glud Eva, Christensen Lise, Blaakaer Jan, Vuust Jens, Bock Johannes E, Norgaard-Pedersen Bent, Hogdall Claus K

机构信息

Institute of Cancer Epidemiology, Danish Cancer Society, Laboratory of Molecular Biology, Statens Serum Institut, Copenhagen, Denmark.

出版信息

Anticancer Res. 2003 Jul-Aug;23(4):3397-404.

PMID:12926080

Abstract

BACKGROUND

The p53 gene is frequently mutated in various human tumours. In addition, single nucleotide polymorphisms are often observed in exons and introns of the p53 gene in normal tissues and tumours.

MATERIALS AND METHODS

A total of 210 blood and tissue samples from 182 ovarian cancers (OC) and 28 ovarian borderline tumours, in addition to blood samples from 72 healthy women, were analysed. The used analyses were PCR and SSCP. The distinguishable SSCP patterns were confirmed by DNA sequencing.

RESULTS

A polymorphism located at position 38 in intron 2 of the p53 gene was studied in blood and tumour tissues from Danish ovarian tumour patients and in blood from controls. Significant differences were found between the distributions of the genotypes in blood samples compared to the corresponding tissue samples (p = 0.0002). A tendency towards a significant difference in survival was observed between OC stage II patients with a shift from one genotype in the blood to another genotype in the tissue and patients with no shift (p = 0.05). In multivariate COX regression analysis restricted to stage III OC patients, the only independent factors found were shift, serum-tetranectin and age.

CONCLUSION

A shift from one p53 intron 2 genotype in the blood to another genotype in the tissue may be a prognostic factor in ovarian cancer patients.

摘要

背景

p53基因在多种人类肿瘤中经常发生突变。此外，在正常组织和肿瘤中，p53基因的外显子和内含子中经常观察到单核苷酸多态性。

材料与方法

分析了来自182例卵巢癌（OC）和28例卵巢交界性肿瘤的210份血液和组织样本，以及72名健康女性的血液样本。所采用的分析方法为聚合酶链反应（PCR）和单链构象多态性分析（SSCP）。通过DNA测序确认可区分的SSCP模式。

结果

对丹麦卵巢肿瘤患者的血液和肿瘤组织以及对照组血液中p53基因第2内含子第38位的多态性进行了研究。发现血液样本与相应组织样本中基因型分布存在显著差异（p = 0.0002）。观察到OC II期患者中，血液中一种基因型转变为组织中另一种基因型的患者与未发生转变的患者之间存在生存差异的趋势（p = 0.05）。在仅限于III期OC患者的多变量COX回归分析中，发现的唯一独立因素是基因型转变、血清四连蛋白和年龄。