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


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.


CONCLUSIONS
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.
Høgdall
Estrid V
EV
Institute of Cancer Epidemiology, Danish Cancer Society, Laboratory of Molecular Biology, Statens Serum Institut, Copenhagen, Denmark. hogdall@dadlnet.dk
Kjaer
Susanne K
SK
Glud
Eva
E
Christensen
Lise
L
Blaakaer
Jan
J
Vuust
Jens
J
Bock
Johannes E
JE
Norgaard-Pedersen
Bent
B
Hogdall
Claus K
CK
D000328:Adult; D000368:Aged; D018394:CA-125 Antigen / Q000097:blood; D003276:Contraceptives, Oral / Q000494:pharmacology; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D005838:Genotype; D020073:Gravidity; D006801:Humans; D007438:Introns / Q000235:genetics; D037181:Lectins, C-Type / Q000097:blood; D008875:Middle Aged; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology; D018807:Polymorphism, Single-Stranded Conformational; D011379:Prognosis; D012907:Smoking / Q000235:genetics
D018394:CA-125 Antigen; D003276:Contraceptives, Oral; D037181:Lectins, C-Type; C048648:tetranectin