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Journal of Mammary Gland Biology and Neoplasia

Published in:

01-04-2011

Inherited Mutations in Breast Cancer Genes—Risk and Response

Authors: Andrew Y. Shuen, William D. Foulkes

Published in: Journal of Mammary Gland Biology and Neoplasia | Issue 1/2011

Abstract

Germ-line mutations in BRCA1 and BRCA2 confer a high risk of developing breast cancer. They account, however, for only 40% of strongly familial breast cancer cases. Intensive genome-wide searches for other highly-penetrant BRCA genes that, individually account for a sizeable fraction of the remaining heritability has not identified any plausible candidates. The “missing heritability” is thought to be due to cumulative effects of susceptibility alleles associated with low to moderate penetrance, in accordance with a polygenic model of inheritance. In addition, a large number of individually very rare, highly penetrant variants could account for part of the gap. Meanwhile, an understanding of the function of BRCA1 and BRCA2 in the DNA damage response pathway has lead to the identification of a number of breast cancer susceptibility genes including PALB2, CHEK2, ATM and BRIP1, all of which interact directly or indirectly with BRCA1 or BRCA2. Knowledge of how BRCA1 and BRCA2 maintain genomic integrity has also led the development of novel targeted therapies. Here we summarize the recent advances made in the understanding of the functions of these two genes, as well as the risks and responses associated with mutations in these and other breast cancer susceptibility genes.

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Title: Inherited Mutations in Breast Cancer Genes—Risk and Response
Authors: Andrew Y. Shuen
William D. Foulkes
Publication date: 01-04-2011
Publisher: Springer US
Published in: Journal of Mammary Gland Biology and Neoplasia / Issue 1/2011
Print ISSN: 1083-3021
Electronic ISSN: 1573-7039
DOI: https://doi.org/10.1007/s10911-011-9213-5

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