The genetic and epigenetic landscape of early-onset colorectal cancer

Abstract

Colorectal cancer (CRC) in individuals under the age of 50 is a problem that is increasing in USA and around the world. In this review, we discuss the degree to which early-onset (EO)CRC may be due to unsuspected Lynch syndrome or other inherited germline variants that predispose to cancer, describe the known somatic genetic alterations in EO tumors and discuss alterations in DNA methylation. Approximately 20% of EOCRCs can be attributed to identifiable germline mutations in genes that cause familial cancer syndromes. A variety of other genetic/epigenetic alterations have also been reported. We conclude that this is a heterogeneous problem, that requires a comprehensive analysis of genetic/epigenetic signatures to better understand EOCRC. Various subsets of EOCRCs must be analyzed individually for clues regarding the etiologies and possible specific therapies for this disease.

Keywords::

• early-onset colorectal cancer
• epigenetics
• familial cancer
• genetics
• LINE-1 hypomethylation
• Lynch syndrome

Financial & competing interests disclosure

This research was funded by NIH grant number R01 CA072851 (Familial and Early-Onset Colorectal Cancer). CR Boland is a consultant for Ambry Genetics. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

This research was funded by NIH grant number R01 CA072851 (Familial and Early-Onset Colorectal Cancer). CR Boland is a consultant for Ambry Genetics. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.