Communicated by Michael Dean
Rare germline mutations in PALB2 and breast cancer risk: A population-based study†
Article first published online: 15 FEB 2012
© 2012 Wiley Periodicals, Inc.
Special Issue: Focus on the NIH Undiagnosed Diseases Program
Volume 33, Issue 4, pages 674–680, April 2012
How to Cite
Tischkowitz, M., Capanu, M., Sabbaghian, N., Li, L., Liang, X., Vallée, M. P., Tavtigian, S. V., Concannon, P., Foulkes, W. D., Bernstein, L., The WECARE Study Collaborative Group, Bernstein, J. L. and Begg, C. B. (2012), Rare germline mutations in PALB2 and breast cancer risk: A population-based study. Hum. Mutat., 33: 674–680. doi: 10.1002/humu.22022
- Issue published online: 12 MAR 2012
- Article first published online: 15 FEB 2012
- Accepted manuscript online: 12 JAN 2012 12:00AM EST
- Manuscript Accepted: 22 DEC 2011
- Manuscript Received: 3 OCT 2011
- Jewish General Hospital Weekend to End Breast Cancer; the Quebec Ministry of Economic Development, the Innovation and Export Trade, and the Jodi Taiger Lazarus Fund for Hereditary Breast Cancer Research; Fonds de la Recherche en Santé du Québec (FRSQ) clinician-scientist award (to M.T.); National Cancer Institute. Grant Number: CA131010, R01 CA097397, U01 CA083178
- breast cancer;
Germline mutations in the PALB2 gene are associated with an increased risk of developing breast cancer but little is known about the frequencies of rare variants in PALB2 and the nature of the variants that influence risk. We selected participants recruited to the Women's Environment, Cancer, and Radiation Epidemiology (WECARE) Study and screened lymphocyte DNA from cases with contralateral breast cancer (n = 559) and matched controls with unilateral breast cancer (n = 565) for PALB2 mutations. Five pathogenic PALB2 mutations were identified among the cases (0.9%) versus none among the controls (P = 0.04). The first-degree female relatives of these five carriers demonstrated significantly higher incidence of breast cancer than relatives of noncarrier cases, indicating that pathogenic PALB2 mutations confer an estimated 5.3-fold increase in risk (95% CI: 1.8–13.2). The frequency of rare (<1% MAF) missense mutations was similar in both groups (23 vs. 21). Our findings confirm in a population-based study setting of women with breast cancer the strong risk associated with truncating mutations in PALB2 that has been reported in family studies. Conversely, there is no evidence from this study that rare PALB2 missense mutations strongly influence breast cancer risk. Hum Mutat 33:674–680, 2012. © 2012 Wiley Periodicals, Inc.