Rare germline mutations in PALB2 and breast cancer risk: A population-based study Journal Article
| Authors: | 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.; Begg, C. B. |
| Contributors: | Reiner, A. S.; Orlow, I. |
| Article Title: | Rare germline mutations in PALB2 and breast cancer risk: A population-based study |
| 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. © 2012 Wiley Periodicals, Inc. |
| Keywords: | adult; controlled study; middle aged; carrier protein; unclassified drug; gene mutation; major clinical study; missense mutation; case-control studies; mutation, missense; cancer risk; genetic predisposition to disease; breast cancer; incidence; introns; breast neoplasms; brca2 protein; nuclear proteins; nucleotide sequence; tumor suppressor proteins; lymphocyte; germ-line mutation; cell dna; contralateral; palb2 protein; palb2; contralateral breast cancer; unilateral breast cancer; case-control |
| Journal Title: | Human Mutation |
| Volume: | 33 |
| Issue: | 4 |
| ISSN: | 1059-7794 |
| Publisher: | Wiley Liss |
| Date Published: | 2012-04-01 |
| Start Page: | 674 |
| End Page: | 680 |
| Language: | English |
| DOI: | 10.1002/humu.22022 |
| PROVIDER: | scopus |
| PUBMED: | 22241545 |
| PMCID: | PMC3767757 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 2 April 2012" - "CODEN: HUMUE" - "Source: Scopus" |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work