PALB2 (Partner and Localizer of BRCA2) is a tumor suppressor gene encoding the PALB2 protein. The PALB2 protein binds and stabilizes the BRCA2 protein, allowing it to repair DNA in the same DNA damage response pathway as BRCA1. Single allele germline loss-of-function mutations in PALB2 are associated with an increased risk of breast cancer and pancreatic cancer, and biallelic mutations lead to a Fanconi anemia complementation group, [FANCN]]. PALB2 mutations have intermediate penetrance, with carriers having about a two- to four-fold increased risk of developing breast cancer compared with the general population. These risk estimates may be higher in patients with a family history of breast cancer.
PALB2 (partner and localizer of BRCA2) is a tumor suppressor gene which encodes for the PALB2 protein, which interacts with the protein produced by the BRCA2 gene. The PALB2 protein stabilizes the BRCA2 protein, allowing the BRCA2 protein to repair DNA double-strand breaks by a process known as homologous recombination. Monoallelic germline loss-of-function mutations in PALB2 are associated with an increased risk of breast and pancreatic cancer and biallelic mutations lead to a Fanconi anemia complementation group, designated subtype N (FANCN). Most pathogenic PALB2 mutations that have been detected are truncating frameshift or stop codons and are scattered throughout the entire gene region, without hot-spot areas.
[PMID 25099575] This paper 'Breast-Cancer Risk in Families with Mutations in PALB2' (N Engl J Med 2014; 371:497-506) analyzed the risk of breast cancer among 362 members of 154 families who had deleterious truncating, splice, or deletion mutations in PALB2. The age-specific breast-cancer risk for mutation carriers was estimated with the use of a modified segregation-analysis approach that allowed for the effects of PALB2 genotype and residual familial aggregation. The risk of breast cancer for female PALB2 mutation carriers, as compared with the general population, was eight to nine times as high among those younger than 40 years of age, six to eight times as high among those 40 to 60 years of age, and five times as high among those older than 60 years of age. The estimated cumulative risk of breast cancer among female mutation carriers was 14% (95% confidence interval [CI], 9 to 20) by 50 years of age and 35% (95% CI, 26 to 46) by 70 years of age. Breast-cancer risk was also significantly influenced by birth cohort (P<0.001) and by other familial factors (P=0.04). The absolute breast-cancer risk for PALB2 female mutation carriers by 70 years of age ranged from 33% (95% CI, 25 to 44) for those with no family history of breast cancer to 58% (95% CI, 50 to 66) for those with two or more first-degree relatives with breast cancer at 50 years of age.
- rs180177102 - the most common, apparently, even though even it is quite rare
and more exhaustively:
|dbSNP rs-id||Coding Change|