BRCA1 and BRCA2 mutations in ethnic lebanese Arab womenwith high hereditary risk breast cancer

Abstract

Purpose. Breast cancer is the most common malignancy among women in Lebanon and in Arab countries, with 50% of cases presenting before the age of 50 years. Methods. Between 2009 and 2012, 250 Lebanesewomenwith breastcancerwhowereconsideredtobeat high riskofcarrying BRCA1 or BRCA2 mutations because of presentation at young age and/or positive family history (FH) of breast or ovarian cancer were recruited. Clinical data were analyzed statistically. Coding exons andintron-exonboundaries ofBRCA1andBRCA2 were sequenced from peripheral blood DNA. All patients were tested for BRCA1 rearrangements using multiplex ligationdependent probe amplification (MLPA). BRCA2 MLPA was done in selected cases. Results. Overall, 14 of250 patients (5.6%) carried a deleterious BRCA mutation (7 BRCA1, 7 BRCA2) and 31 (12.4%) carried a variant of uncertain significance. Eight of 74 patients (10.8%) aged ≤40 years with positive FH and only 1 of 74 patients (1.4%)aged ≤40 years without FH had a mutated BRCA. Fourof 75 patients (5.3%) aged 41–50 years with FH had a deleterious mutation. Only 1 of 27 patients aged > 50 years at diagnosis had aBRCAmutation. All seven patients withBRCA1mutations had grade 3 infiltrating ductal carcinoma and triple-negative breast cancer. Nine BRCA1 and 17 BRCA2 common haplotypes were observed. Conclusion. Prevalence ofdeleteriousBRCAmutations is lower than expected and does not support the hypothesis that BRCA mutations alone cause the observed high percentage of breast cancer in youngwomenof Lebanese and Arab descent. Studies to search for other genetic mutations are recommended. © AlphaMed Press 2015.