Journal article
Rare, evolutionarily unlikely missense substitutions in CHEK2 contribute to breast cancer susceptibility: Results from a breast cancer family registry case-control mutation-screening study
F Le Calvez-Kelm, F Lesueur, F Damiola, M Vallée, C Voegele, D Babikyan, G Durand, N Forey, S McKay-Chopin, N Robinot, T Nguyen-Dumont, A Thomas, GB Byrnes, JL Hopper, MC Southey, IL Andrulis, EM John, SV Tavtigian
Breast Cancer Research | Published : 2011
DOI: 10.1186/bcr2810
Abstract
Introduction: Both protein-truncating variants and some missense substitutions in CHEK2 confer increased risk of breast cancer. However, no large-scale study has used full open reading frame mutation screening to assess the contribution of rare missense substitutions in CHEK2 to breast cancer risk. This absence has been due in part to a lack of validated statistical methods for summarizing risk attributable to large numbers of individually rare missense substitutions.Methods: Previously, we adapted an in silico assessment of missense substitutions used for analysis of unclassified missense substitutions in BRCA1 and BRCA2 to the problem of assessing candidate genes using rare missense substi..
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Awarded by Canadian Institutes of Health Research
Funding Acknowledgements
We thank David Goldgar for help with familial relative risk calculations and note that a Microsoft Excel-based familial relative risk calculator is available from him at david.goldgar@hsc.utah.edu. We also thank James McKay for help with mutation screening amplicon design and Mia Hashibe and Deborah Neklason for helpful comments on the manuscript. This work was supported by the National Cancer Institute, National Institutes of Health (NIH) grant R01 CA121245, and Canadian Institute for Health Research (CIHR) grant CRN-87521-IC089832. The Breast CFR was funded by the NIH under RFA-CA-06-503 and through cooperative agreements with Breast CFR members, including Cancer Care Ontario (U01 CA69467), the Northern California Cancer Center (U01 CA69417) and the University of Melbourne (U01 CA69638). The content of this article does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast CFR, nor does the mention of trade names, commercial products or organizations imply endorsement by the U.S. government or the Breast CFR.