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Clinical Cancer Genomics 

Clinical Cancer Genomics
Chapter:
Clinical Cancer Genomics
Author(s):

Joanne Ngeow

and Charis Eng

DOI:
10.1093/med/9780199896028.003.0036
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date: 29 May 2020

The ultimate goal in oncology is to markedly decrease death from cancer. The past 50 years of research have demonstrated that the architecture of inherited genetic susceptibility to cancers is defined by a collage of predisposition alleles with different levels of risk and prevalence in the population. Improved detection of patients harboring deleterious mutations has allowed for tailored gene-enabled management both in terms of novel targeted therapy as well as a targeted surveillance approach for affected individuals. However, technology continues to move apace, dramatically reducing costs and making genome sequencing fairly routine. The optimal management of low to moderately penetrant genes conferring modestly increased relative risks remains incompletely defined. The next frontier would be to determine what the modifiers of specific risks for Mendelian high penetrance alleles are and to better understand how low penetrance susceptibility alleles cross talk with one another to allow for greater precision in risk prediction. Additionally, recent efforts such as the Collaborative Oncological Gene-environment Study (COGS) recently shed light on new genetic susceptibility loci for breast, ovarian and prostate cancers. These newly identified susceptibility loci explain an increasing proportion of the familial risk of these cancers. Understanding the biological basis of how these germline susceptibility genes interact with somatically acquired alterations will be key to ongoing efforts for novel cancer prevention and therapeutic strategies.

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