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.
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