Penetrance analysis of the PALB2 c.1592deIT founder mutation

Hannele Erkko, James G. Dowty, Jenni Nikkilä, Kirsi Syrjäkoski, Arto Mannermaa, Katri Pylkäs, Melissa C. Southey, Kaija Holli, Anne Kallioniemi, Arja Jukkola-Vuorinen, Vesa Kataja, Veli Matti Kosma, Bing Xia, David M. Livingston, Robert Winqvist, John L. Hopper

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83 Scopus citations


Purpose: PALB2 is a recently identified breast cancer susceptibility gene. We have previously identified in the Finnish population a PALB2 c.1592deIT 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.1592delTwith regard to susceptibility to breast and other forms of cancer. Experimental Design: 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% Cl), 2.2-17.2; P = 0.01] equivalent to a 40% (95% Cl, 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% Cl, 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.

Original languageEnglish (US)
Pages (from-to)4667-4671
Number of pages5
JournalClinical Cancer Research
Issue number14
StatePublished - Jul 15 2008
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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