Int J Med Sci 2008; 5(4):197-202. doi:10.7150/ijms.5.197 This issue Cite
Research Paper
1. Laboratoire Diagnostic Génétique et Moléculaire, Centre Jean Perrin, 58 rue Montalembert, 63011 Clermont-Ferrand, France
2. Service de Sénologie, Centre Pierre et Marie Curie, 1 Avenue Battendier, Algiers, Algeria
3. Institut Claudius Regaud, 20 rue du Pont St Pierre, 31052 Toulouse, France.
Breast cancer rates and median age of onset differ between Western Europe and North Africa. In Western populations, 5 to 10 % of breast cancer cases can be attributed to major genetic factors such as BRCA1 and BRCA2, while this attribution is not yet well defined among Africans. To help determine the contribution of BRCA1 mutations to breast cancer in a North African population, we analysed genomic DNA from breast cancer cases ascertained in Algiers.
Both familial cases (at least three breast cancers in the same familial branch, or two with one bilateral or diagnosed before age 40) and sporadic cases less than 38 years of age were studied. Complete sequencing plus quantitative analysis of the BRCA1 gene was performed. 9.8 % (5/51) of early-onset sporadic and 36.4 % (4/11) of familial cases were found to be associated with BRCA1 mutations. This is in contrast 10.3 % of French HBOC families exhibiting a BRCA1 mutation. One mutation, c.798_799delTT, was observed in two Algerian families and in two families from Tunisia, suggesting a North African founder allele. Algerian non-BRCA1 tumors were of significantly higher grade than French non-BRCA tumors, and the age at diagnosis for Algerian familial cases was much younger than that for French non-BRCA familial cases. In conclusion, we observed a much higher frequency of BRCA1 mutations among young breast cancer patients than observed in Europe, suggesting biological differences and that the inclusion criterea for analysis in Western Europe may not be applicable for the Northern African population.
Keywords: breast cancer, familial cancer syndromes, BRCA1 mutation