PALB2, which encodes a BRCA2-interacting protein, is a breast cancer susceptibility gene.
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.
Rahman
Nazneen
N
Section of Cancer Genetics, Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey SM2 5NG, UK. nazneen.rahman@icr.ac.uk
Seal
Sheila
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Thompson
Deborah
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Kelly
Patrick
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Renwick
Anthony
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Elliott
Anna
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Reid
Sarah
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Spanova
Katarina
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Barfoot
Rita
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Chagtai
Tasnim
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Jayatilake
Hiran
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McGuffog
Lesley
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Hanks
Sandra
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Evans
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Eccles
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Easton
Douglas F
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Stratton
Michael R
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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*
D024682:BRCA2 Protein; D000076164:Fanconi Anemia Complementation Group N Protein; D009687:Nuclear Proteins; C512790:PALB2 protein, human; D025521:Tumor Suppressor Proteins