Truncating mutations in the Fanconi anemia J gene BRIP1 are low-penetrance breast cancer susceptibility alleles.
We identified constitutional truncating mutations of the BRCA1-interacting helicase BRIP1 in 9/1,212 individuals with breast cancer from BRCA1/BRCA2 mutation-negative families but in only 2/2,081 controls (P = 0.0030), and we estimate that BRIP1 mutations confer a relative risk of breast cancer of 2.0 (95% confidence interval = 1.2-3.2, P = 0.012). Biallelic BRIP1 mutations were recently shown to cause Fanconi anemia complementation group J. Thus, inactivating truncating mutations of BRIP1, similar to those in BRCA2, cause Fanconi anemia in biallelic carriers and confer susceptibility to breast cancer in monoallelic carriers.
Seal
Sheila
S
Section of Cancer Genetics, Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey, SM2 5NG, UK.
Thompson
Deborah
D
Renwick
Anthony
A
Elliott
Anna
A
Kelly
Patrick
P
Barfoot
Rita
R
Chagtai
Tasnim
T
Jayatilake
Hiran
H
Ahmed
Munaza
M
Spanova
Katarina
K
North
Bernard
B
McGuffog
Lesley
L
Evans
D Gareth
DG
Eccles
Diana
D
Easton
Douglas F
DF
Stratton
Michael R
MR
Rahman
Nazneen
N
D000328:Adult; D001943:Breast Neoplasms / Q000235:genetics*; D018389:Codon, Nonsense; D004268:DNA-Binding Proteins / Q000235:genetics*; D051856:Fanconi Anemia Complementation Group Proteins / Q000235:genetics*; D005787:Gene Frequency; D006580:Genetic Carrier Screening; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D010375:Pedigree; D019683:Penetrance; D020365:RNA Helicases / Q000235:genetics*
D018389:Codon, Nonsense; D004268:DNA-Binding Proteins; D051856:Fanconi Anemia Complementation Group Proteins; C000618935:BRIP1 protein, human; D020365:RNA Helicases