title: A high frequent BRCA1 founder mutation identified in the Greenlandic population.
abstract: Approximately 10% of all breast and ovarian cancers are dominantly inherited and mutations are mainly found in the BRCA 1 and 2 genes. The penetrance of BRCA1 mutations is reported to be between 68 and 92% and confers a 36-92% life time risk of breast cancer. Most mutations in BRCA1 are uniquely occurring mutations, but founder mutations have been described. In this study we describe a founder mutation with wide spread presence in the Inuit population. We have screened 2,869 persons from Greenland for the presence of a BRCA1 mutation (p.Cys39Gly) only found in the Inuit population. The overall carrier frequency was 1.6% in the general population, but the frequency differs geographically from 0.6% on the West coast to 9.7% in the previously isolated population of the East coast. This is to our knowledge the highest population frequency of a BRCA1 mutation ever to be described. To determine the clinical relevance of the mutation, we have examined ten breast cancer patients and nine ovarian cancer patients from Greenland for the presence of the p.Cys39Gly mutation. We found three ovarian cancer patients (33%) and one breast cancer patient (10%) carrying the mutation. The high number of women carrying a BRCA1 mutation known to trigger the development of potentially lethal diseases leads us to recommend an offer of genetic counselling and test for the mutation to all females of Inuit origin, thereby hopefully preventing a number of breast and ovarian cancer deaths.
authors.affiliation: Department of Cellular and Molecular Medicine, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen N, Denmark. larribaharboe@gmail.com
authors.forename: Theresa Larriba
authors.initials: TL
authors.lastname: Harboe
authors.forename: Hans
authors.initials: H
authors.lastname: Eiberg
authors.forename: Peder
authors.initials: P
authors.lastname: Kern
authors.forename: Bent
authors.initials: B
authors.lastname: Ejlertsen
authors.forename: Lotte
authors.initials: L
authors.lastname: Nedergaard
authors.forename: Vera
authors.initials: V
authors.lastname: Timmermans-Wielenga
authors.forename: Inge-Merete
authors.initials: IM
authors.lastname: Nielsen
authors.forename: Marie Luise
authors.initials: ML
authors.lastname: Bisgaard
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D018703:Founder Effect; D019398:Genes, BRCA1; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006116:Greenland; D006801:Humans; D004930:Inuit / Q000235:genetics; D009154:Mutation; D010051:Ovarian Neoplasms / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length