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Inherited Genetic Susceptibility to Breast Cancer

The American Journal of Pathology, ISSN: 0002-9440, Vol: 183, Issue: 4, Page: 1038-1051
2013
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Review Description

Genome-wide association studies have identified 72 loci associated with breast cancer susceptibility. Seventeen of these are known to predispose to other cancers. High-penetrance susceptibility loci for breast cancer usually result from coding alterations, principally in genes involved in DNA repair, whereas almost all of the associations identified through genome-wide association studies are found in noncoding regions of the genome and are likely to involve regulation of genes in multiple pathways. However, the genes underlying most associations are not yet known. In this review, we summarize the findings from genome-wide association studies in breast cancer and describe the genes and mechanisms that are likely to be involved in the tumorigenesis process. We also discuss approaches to fine-scale mapping of susceptibility regions used to identify the likely causal variant(s) underlying the associations, a major challenge in genetic epidemiology. Finally, we discuss the potential impact of such findings on personalized medicine and future avenues for screening, prediction, and prevention programs.

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