Highlights
- •Contribution of high and moderate penetrant genes to ovarian cancer heritability
- •Contribution of common low risk alleles to ovarian cancer heritability
- •Implications of genetic risk discovery for clinical risk prediction and prevention
Abstract
Epithelial ovarian cancer (EOC) is a heterogeneous disease with a major heritable
component. The different histotypes of invasive disease – high grade serous, clear
cell, endometrioid and mucinous – are associated with different underlying genetic
susceptibility and epidemiological and lifestyle risk factors, all of which contribute
to the different biology and clinical characteristics of each histotype. A combination
of familial and population based sequencing studies, and genome wide association studies
(GWAS) have identified a range of genetic susceptibility alleles for EOC comprising
rare but highly penetrant genes (e.g. BRCA1, BRCA2) that are responsible for familial clustering of ovarian cancer cases; more moderate
penetrance susceptibility genes (e.g. BRIP1, RAD51C/D, MSH6); and multiple common but low penetrance susceptibility alleles identified by GWAS.
Identifying genetic risk alleles for ovarian cancer has had a significant impact on
disease prevention strategies; for example it is now routine clinical practice for
individuals with germline BRCA1 and BRCA2 mutations to undergo risk reducing salpingo-oophorectomy. Because ovarian cancers
are commonly diagnosed at a late clinical stage when the prognosis is poor, the continued
development of genetic risk prediction and prevention strategies will represent an
important approach to reduce mortality due to ovarian cancer. Advances in genomics
technologies that enable more high-throughput genetic testing, combined with research
studies that identify additional EOC risk alleles will likely provide further opportunities
to establish polygenic risk prediction approaches, based on combinations of rare high/moderate
penetrance susceptibility genes and common, low penetrance susceptibility alleles.
This article reviews the current literature describing the genetic and epidemiological
components of ovarian cancer risk, and discusses both the opportunities and challenges
in using this information for clinical risk prediction and prevention.
Keywords
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Article info
Publication history
Published online: October 17, 2017
Accepted:
October 2,
2017
Received in revised form:
September 28,
2017
Received:
May 16,
2017
Identification
Copyright
© 2017 Published by Elsevier Inc.
