title: Penetrance analysis of the PALB2 c.1592delT founder mutation.
abstract: OBJECTIVE
  PALB2 is a recently identified breast cancer susceptibility gene. We have previously identified in the Finnish population a PALB2 c.1592delT founder truncation mutation that is associated with an increased risk of breast cancer. In the present study, we wanted to assess in more detail the increased risk (hazard ratio, HR) and the age-specific cumulative risk (penetrance) of c.1592delT with regard to susceptibility to breast and other forms of cancer.
  
  
  METHODS
  Modified segregation analyses fitted under maximum likelihood theory were used to estimate age-specific cumulative risks and HRs using the families of mutation carriers identified from a consecutive series of breast cancer cases unselected for age at onset or family history.
  
  
  RESULTS
  We found a substantially increased risk of breast cancer [HR, 6.1; 95% confidence interval (95% CI), 2.2-17.2; P = 0.01] equivalent to a 40% (95% CI, 17-77) breast cancer risk by age 70 years, comparable to that for carriers of mutations in BRCA2. We found marginal evidence (P = 0.06) that the HR for breast cancer decreased with age by 4.2% per year (95% CI, 0.2-8.1), from 7.5-fold at age 30 years to 2.0-fold at age 60 years.
  
  
  CONCLUSIONS
  Our results suggest that it may be appropriate to offer PALB2 c.1592delT mutation testing to Finnish women with breast cancer, especially those with an early age at onset or a family history of breast or related cancers, and to offer carriers the option of participation in extended disease surveillance programs.
authors.affiliation: Laboratory of Cancer Genetics, Oulu University Hospital, Finland.
authors.forename: Hannele
authors.initials: H
authors.lastname: Erkko
authors.forename: James G
authors.initials: JG
authors.lastname: Dowty
authors.forename: Jenni
authors.initials: J
authors.lastname: Nikkilä
authors.forename: Kirsi
authors.initials: K
authors.lastname: Syrjäkoski
authors.forename: Arto
authors.initials: A
authors.lastname: Mannermaa
authors.forename: Katri
authors.initials: K
authors.lastname: Pylkäs
authors.forename: Melissa C
authors.initials: MC
authors.lastname: Southey
authors.forename: Kaija
authors.initials: K
authors.lastname: Holli
authors.forename: Anne
authors.initials: A
authors.lastname: Kallioniemi
authors.forename: Arja
authors.initials: A
authors.lastname: Jukkola-Vuorinen
authors.forename: Vesa
authors.initials: V
authors.lastname: Kataja
authors.forename: Veli-Matti
authors.initials: VM
authors.lastname: Kosma
authors.forename: Bing
authors.initials: B
authors.lastname: Xia
authors.forename: David M
authors.initials: DM
authors.lastname: Livingston
authors.forename: Robert
authors.initials: R
authors.lastname: Winqvist
authors.forename: John L
authors.initials: JL
authors.lastname: Hopper
mesh_terms: D000328:Adult; D017677:Age Distribution; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics*; D000076164:Fanconi Anemia Complementation Group N Protein; D005260:Female; D005387:Finland / Q000453:epidemiology; D018703:Founder Effect; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D010375:Pedigree; D019683:Penetrance; D012307:Risk Factors; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D000076164:Fanconi Anemia Complementation Group N Protein; D009687:Nuclear Proteins; C512790:PALB2 protein, human; D025521:Tumor Suppressor Proteins