BRCA1 mutations in South African breast and/or ovarian cancer families: Evidence of a novel founder mutation in Afrikaner families

• Published in: International journal of cancer 2004-07, Vol.110 (5), p.677-682
• Main Authors: Reeves, Michelle D., Yawitch, Tali M., van der Merwe, Nerina C., van den Berg, Hester J., Dreyer, Greta, van Rensburg, Elizabeth J.
• Format: Article
• Language: English
• Subjects: Adult; Biological and medical sciences; BRCA1; breast cancer; Breast Neoplasms - genetics; Carcinoma - genetics; DNA Mutational Analysis; European Continental Ancestry Group; Fallopian Tube Neoplasms - genetics; Family Health; Female; Female genital diseases; Founder Effect; founder mutation; Genes, BRCA1; Genotype; Germ-Line Mutation; Gynecology. Andrology. Obstetrics; Humans; Introns; Mammary gland diseases; Medical sciences; Middle Aged; Mutation; Mutation, Missense; Ovarian Neoplasms - genetics; Polymerase Chain Reaction; Polymorphism, Single-Stranded Conformational; South Africa; Tropical medicine; Tumors
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.20186

Germ‐line mutations within BRCA1 are responsible for different proportions of inherited susceptibility to breast/ovarian cancer, and the spectrum of mutations within this gene is often unique to certain populations. At this time, there have been no reports regarding the role of BRCA1 in South African breast and/or ovarian cancer families. We therefore screened 90 South African breast/ovarian cancer families for BRCA1 mutations by means of PCR‐based mutation detection assays. Eighteen families (20%) were identified with BRCA1 disease‐causing mutations. Four Ashkenazi Jewish families were identified with the 185delAG mutation, whereas 2 Afrikaner and 1 Ashkenazi Jewish family were found to harbor the 5382insC mutation. Five of the families (5.56%), all of whom are Afrikaners, were found to carry the novel E881X mutation. Genotype analyses show that these patients share a common ancestor. Genealogic studies have identified 3 possible founding couples for this mutation, all of whom arrived in the Cape from France in the late 1600s. Of the remaining mutations detected, 3 have not been reported previously and include the S451X, 1493delC (detected twice) and 4957insC mutations. © 2004 Wiley‐Liss, Inc.