title: Truncating mutations in the Fanconi anemia J gene BRIP1 are low-penetrance breast cancer susceptibility alleles.
abstract: 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.
authors.affiliation: Section of Cancer Genetics, Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey, SM2 5NG, UK.
authors.forename: Sheila
authors.initials: S
authors.lastname: Seal
authors.forename: Deborah
authors.initials: D
authors.lastname: Thompson
authors.forename: Anthony
authors.initials: A
authors.lastname: Renwick
authors.forename: Anna
authors.initials: A
authors.lastname: Elliott
authors.forename: Patrick
authors.initials: P
authors.lastname: Kelly
authors.forename: Rita
authors.initials: R
authors.lastname: Barfoot
authors.forename: Tasnim
authors.initials: T
authors.lastname: Chagtai
authors.forename: Hiran
authors.initials: H
authors.lastname: Jayatilake
authors.forename: Munaza
authors.initials: M
authors.lastname: Ahmed
authors.forename: Katarina
authors.initials: K
authors.lastname: Spanova
authors.forename: Bernard
authors.initials: B
authors.lastname: North
authors.forename: Lesley
authors.initials: L
authors.lastname: McGuffog
authors.forename: D Gareth
authors.initials: DG
authors.lastname: Evans
authors.forename: Diana
authors.initials: D
authors.lastname: Eccles
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Easton
authors.forename: Michael R
authors.initials: MR
authors.lastname: Stratton
authors.forename: Nazneen
authors.initials: N
authors.lastname: Rahman
mesh_terms: 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*
chemical_list: D018389:Codon, Nonsense; D004268:DNA-Binding Proteins; D051856:Fanconi Anemia Complementation Group Proteins; C000618935:BRIP1 protein, human; D020365:RNA Helicases