title: PALB2, which encodes a BRCA2-interacting protein, is a breast cancer susceptibility gene.
abstract: PALB2 interacts with BRCA2, and biallelic mutations in PALB2 (also known as FANCN), similar to biallelic BRCA2 mutations, cause Fanconi anemia. We identified monoallelic truncating PALB2 mutations in 10/923 individuals with familial breast cancer compared with 0/1,084 controls (P = 0.0004) and show that such mutations confer a 2.3-fold higher risk of breast cancer (95% confidence interval (c.i.) = 1.4-3.9, P = 0.0025). The results show that PALB2 is a breast cancer susceptibility gene and further demonstrate the close relationship of the Fanconi anemia-DNA repair pathway and breast cancer predisposition.
authors.affiliation: Section of Cancer Genetics, Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey SM2 5NG, UK. nazneen.rahman@icr.ac.uk
authors.forename: Nazneen
authors.initials: N
authors.lastname: Rahman
authors.forename: Sheila
authors.initials: S
authors.lastname: Seal
authors.forename: Deborah
authors.initials: D
authors.lastname: Thompson
authors.forename: Patrick
authors.initials: P
authors.lastname: Kelly
authors.forename: Anthony
authors.initials: A
authors.lastname: Renwick
authors.forename: Anna
authors.initials: A
authors.lastname: Elliott
authors.forename: Sarah
authors.initials: S
authors.lastname: Reid
authors.forename: Katarina
authors.initials: K
authors.lastname: Spanova
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: Lesley
authors.initials: L
authors.lastname: McGuffog
authors.forename: Sandra
authors.initials: S
authors.lastname: Hanks
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
mesh_terms: D000328:Adult; D024682:BRCA2 Protein / Q000502:physiology; D001943:Breast Neoplasms / Q000235:genetics*; D000076164:Fanconi Anemia Complementation Group N Protein; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D010375:Pedigree; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D024682:BRCA2 Protein; D000076164:Fanconi Anemia Complementation Group N Protein; D009687:Nuclear Proteins; C512790:PALB2 protein, human; D025521:Tumor Suppressor Proteins