Two biallelic polymorphisms in introns 3 and 6 of the p53 gene were analysed for a possible risk-modifying effect for ovarian cancer.
Germline DNA was genotyped from 310 German Caucasian ovarian cancer patients and 364 healthy controls.
We also typed 124 affected and 276 unaffected female carriers with known deleterious BRCA1 or BRCA2 germline mutation from high-risk breast-ovarian cancer families.
Genotyping was based on PCR and high-resolution gel electrophoresis.
German ovarian cancer patients who carried the rare allele of the Mspl restriction fragment length polymorphism (RELP) in intron 6 were found to have an overall 1.93-fold increased risk (95% confidence internal (CI) 1.27-2.91) which further increased with the age at diagnosis of 41-60 years (odds ratio (OR) 2.71,95% CI 1.10-6.71 for 41-50 and OR 2.44,95% Cl 1.12-5.28 for 51-60).
The 16 bp duplication polymorphism in intron 3 was in a strong linkage to the Mspl RFLP.
In BRCA1 or BRCA2 mutation carriers, no difference in allele frequency was observed for carriers affected or unaffected with ovarian cancer.
Our data suggest that intronic polymorphisms of the p53 gene modify the risk for ovarian cancer patients but not in carriers with BRCA1 or BRCA2 mutations.
Mots-clés Pascal : Tumeur maligne, Ovaire, Gène suppresseur tumeur, Gène TP53, Variabilité génétique, Mutation, Lignée germinale, Polymorphisme, Facteur risque, Epidémiologie, Etude cas témoin, Allemagne, Europe, Homme, Appareil génital femelle pathologie, Ovaire pathologie, Génétique, Gène BRCA1, Gène BRCA2
Mots-clés Pascal anglais : Malignant tumor, Ovary, Tumor suppressor gene, TP53 Gene, Genetic variability, Mutation, Germ line, Polymorphism, Risk factor, Epidemiology, Case control study, Germany, Europe, Human, Female genital diseases, Ovarian diseases, Genetics
Notice produite par :
Inist-CNRS - Institut de l'Information Scientifique et Technique
Cote : 99-0429125
Code Inist : 002B20C02. Création : 22/03/2000.