Journal article
Rare germline mutations in PALB2 and breast cancer risk: A population-based study
Human mutation, Vol.33(4), pp.674-680
04/2012
DOI: 10.1002/humu.22022
PMCID: PMC3767757
PMID: 22241545
Abstract
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.
Details
- Title: Subtitle
- Rare germline mutations in PALB2 and breast cancer risk: A population-based study
- Creators
- Marc Tischkowitz - Program in Cancer Genetics, Departments of Oncology and Human Genetics, McGill University, Montreal, Quebec, CanadaMarinela Capanu - Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New YorkNelly Sabbaghian - Program in Cancer Genetics, Departments of Oncology and Human Genetics, McGill University, Montreal, Quebec, CanadaLili Li - Program in Cancer Genetics, Departments of Oncology and Human Genetics, McGill University, Montreal, Quebec, CanadaXiaolin Liang - Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New YorkMaxime P Vallée - International Agency for Research on Cancer, Lyon, FranceSean V Tavtigian - Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UtahPatrick Concannon - Department of Biochemistry and Molecular Genetics and Center for Public Health Genomics, University of Virginia, Charlottesville, VirginiaWilliam D Foulkes - Program in Cancer Genetics, Departments of Oncology and Human Genetics, McGill University, Montreal, Quebec, CanadaLeslie Bernstein - Beckman Research Institute, City of Hope, Duarte, CaliforniaJonine L Bernstein - Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New YorkColin B Begg - Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New YorkWECARE Study Collaborative Group
- Contributors
- Charles F Lynch (Contributor) - University of Iowa, Epidemiology
- Resource Type
- Journal article
- Publication Details
- Human mutation, Vol.33(4), pp.674-680
- Publisher
- Wiley Subscription Services, Inc., A Wiley Company
- DOI
- 10.1002/humu.22022
- PMID
- 22241545
- PMCID
- PMC3767757
- ISSN
- 1059-7794
- eISSN
- 1098-1004
- Number of pages
- 7
- Language
- English
- Date published
- 04/2012
- Academic Unit
- Epidemiology
- Record Identifier
- 9984214801502771
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