Two founder BRCA2 mutations predispose to breast cancer in young women.
The mutation spectrum of BRCA1 and BRCA2 presents a wide range of unique mutations in breast/ovarian cancer patients but recurrent mutations with founder effects have also been described. BRCA2 5344delAATA and 9538delAA are recurrent mutations in Castilla-León (Spain) representing 10.6% of BRCA2 positive families. By genotyping eleven chromosome 13 markers (4.3 Mb) we demonstrate that each mutation shows core haplotypes of 1.66 and 0.87 Mb, respectively, supporting a common ancestor in Castilla-León. Furthermore, both mutations are associated with earlier onset of breast cancer (5344delAATA: 37.4 years, P = 0.033; 9538delAA: 39.4 years, P = 0.008). The identification of founder effects improves the genetic screening strategy to be followed and facilitates the clinical management of asymptomatic carriers.
Infante
Mar
M
Genética del Cáncer, Instituto de Biología y Genética Molecular (UVa-CSIC), Sanz y Forés s/n, 47003, Valladolid, Spain.
Durán
Mercedes
M
Lasa
Adriana
A
Acedo
Alberto
A
de la Hoya
Miguel
M
Esteban-Cardeñosa
Eva
E
Sanz
David J
DJ
Pérez-Cabornero
Lucia
L
Lastra
Enrique
E
Miner
Cristina
C
Velasco
Eladio A
EA
D000328:Adult; D017668:Age of Onset; D000368:Aged; D051017:Apoptosis Regulatory Proteins; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D018703:Founder Effect; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D040941:Heredity; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D018570:Risk Assessment; D012307:Risk Factors; D013030:Spain
D051017:Apoptosis Regulatory Proteins; C118024:BLID protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human