Among women of Ashkenazi Jewish origin, a frameshift mutation of the BRCA1 gene, designated 185delAG, occurs with a carrier frequency of approximately 1% and is estimated to account for about 39% of ovarian cancer cases occurring prior to age 50 years.
To determine the actual frequency of this mutation among Jewish women with ovarian cancer, we tested DNA collected as part of an ongoing population-based case-control study of genetic and environmental factors for epithelial ovarian cancer in eastern Massachusetts.
Using single-stranded conformational polymorphism analysis followed by direct sequencing, we found that 6 (19.4%) of 31 Jewish patients were carriers for a 185delAG mutation compared to 0 of 23 Jewish controls (P=0.03).
Using empiric logits, the estimated relative risk for ovarian cancer associated with a 185delAG mutation is 12.0. The average age of the 6 patients with mutations was 48.3 years, significantly younger than the average of 57.4 years observed for the 25 patients without the mutation (P=0.05).
For ovarian cancer diagnosed prior to age 50 years, three (37.5%) of eight patients carried the mutation.
None of the six patients with the mutation had a history consistent with hereditary breast ovarian cancer syndrome, although two had a personal history of prior cancer.
Our results provide empiric confirmation of the estimated prevalence of 185delAG mutations among Jewish women with ovarian cancer.
Mots-clés Pascal : Tumeur maligne, Ovaire, Pathogénie, Mutation, Délétion, Tissu, Facteur risque, Homme, Femelle, Juif, Prédisposition, Epidémiologie moléculaire, Ethnie, Ovaire pathologie, Appareil génital femelle pathologie, Massachusetts, Etats Unis, Amérique du Nord, Amérique, Gène BRCA1
Mots-clés Pascal anglais : Malignant tumor, Ovary, Pathogenesis, Mutation, Deletion, Tissue, Risk factor, Human, Female, Jew, Predisposition, Molecular epidemiology, Ethnic group, Ovarian diseases, Female genital diseases, Massachusetts, United States, North America, America
Notice produite par :
Inist-CNRS - Institut de l'Information Scientifique et Technique
Cote : 96-0194894
Code Inist : 002B20C02. Création : 199608.