Distribution of p53 codon 72 polymorphisms in ovarian tumour patients and their prognostic significance in ovarian cancer patients.
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
The prevalence of a polymorphism involving codon 72 of exon 4 in the p53 gene was studied in peripheral white blood cells and tumour tissues from Danish ovarian tumour patients and in peripheral white blood cells from controls. The analyses were performed by Polymerase Chain Reaction (PCR), Restriction Fragment Length Polymorphism (RFLP) and DNA sequencing. The amino acid residue at this position is either arginine (p53-Arg) or proline (p53-Pro).


RESULTS
There was no correlation between the frequency of the three genotypes (Pro/Pro, Arg/Arg and Arg/Pro) and age, stage or histological type of the tumour. A significant difference in survival was observed between ovarian cancer stage III patients with a shift from one genotype in the blood to another genotype in the tissue and patients with no shift (p=0.0216).


CONCLUSIONS
Kaplan-Meier survival analyses and multivariate Cox regression analysis stratified to stage III ovarian cancer patients showed that a shift from one genotype in the blood to another genotype in the tissue is a prognostic factor in Danish ovarian cancer patients.
Høgdall
Estrid V S
EV
Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen. estrid@cancer.dk
Høgdall
Claus K
CK
Christensen
Lise
L
Glud
Eva
E
Blaakaer
Jan
J
Bock
Johannes E
JE
Vuust
Jens
J
Nørgaard-Pedersen
Bent
B
Kjaer
Susanne K
SK
D000328:Adult; D000368:Aged; D018394:CA-125 Antigen / Q000097:blood; D016022:Case-Control Studies; D003062:Codon; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000097:blood / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011379:Prognosis; D015996:Survival Rate
D018394:CA-125 Antigen; D003062:Codon