Genetic analysis of BRCA1 and BRCA2 in Nigerian breast cancer patients Free

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Germline mutations in the BRCA1 and BRCA2 tumor suppressor genes are highly penetrant for breast/ovarian cancer, and genetic testing is routinely recommended to patients with strong family histories. The contribution of hereditary breast cancers is generally 5-10% of all breast cancer cases, but the frequency and spectrum of BRCA1/2 germline mutations may vary in different ethnic populations. Breast cancer is less common in Africans and African Americans than other populations, yet its occurrence is associated with histopathological features similar to those in BRCA1 mutation carriers. To address whether this similarity results from a distinctive contribution of BRCA1/2-associated disease, we performed complete sequence analysis of the BRCA1 and BRCA2 exons and regions near intron/exon boundaries in a population of Nigerian breast cancer patients unselected for family history or age of disease onset. We identified 17/270 (6.3%, 95% confidence interval (CI) = 3.7%-9.9%) patients heterozygous for one of 10 different deleterious BRCA1 mutations, four of which have never been reported previously. We also identified 4/186 (2.2%, 95% CI = 0.6%-5.4%) patients heterozygous for unique deleterious BRCA2 mutations, three of which have never been reported previously. The mutation rate did not vary with age or menopausal status, though there is a trend toward higher mutation prevalence in patients with positive family history. The frequency of BRCA1 mutations in our Nigerian cohort is the highest we are aware of in populations unselected for family history or age of onset, yet previous reports have suggested the frequency of BRCA1 mutations in African American populations is lower than in other population. To address whether the Nigerian cohort is genetically similar to African American populations, we characterized the BRCA1 tag SNP haplotypes of 189 unaffected Nigerian control subjects, and found four haplotypes shared only between Nigerians and a previously reported African American population. Ongoing work will identify the haplotypes in which the Nigerian population mutations occurred. We conclude that BRCA1 and, to a lesser extent BRCA2, play an important role in breast cancer risk in Nigeria.