Clinical and molecular features of young-onset colorectal cancer

Abstract

Colorectal cancer (CRC) is one of the leading causes of cancer related mortality worldwide. Although young-onset CRC raises the possibility of a hereditary component, hereditary CRC syndromes only explain a minority of young-onset CRC cases. There is evidence to suggest that young-onset CRC have a different molecular profile than late-onset CRC. While the pathogenesis of young-onset CRC is well characterized in individuals with an inherited CRC syndrome, knowledge regarding the molecular features of sporadic young-onset CRC is limited. Understanding the molecular mechanisms of young-onset CRC can help us tailor specific screening and management strategies. While the incidence of late-onset CRC has been decreasing, mainly attributed to an increase in CRC screening, the incidence of young-onset CRC is increasing. Differences in the molecular biology of these tumors and low suspicion of CRC in young symptomatic individuals, may be possible explanations. Currently there is no evidence that supports that screening of average risk individuals less than 50 years of age will translate into early detection or increased survival. However, increasing understanding of the underlying molecular mechanisms of young-onset CRC could help us tailor specific screening and management strategies. The purpose of this review is to evaluate the current knowledge about young-onset CRC, its clinicopathologic features, and the newly recognized molecular alterations involved in tumor progression.

Keywords: Young-onset colorectal cancer, Late-onset colorectal cancer, Microsatellite instability, CpG island methylator phenotype, Chromosomal instability, Microsatellite, Chromosome stable colorectal cancer

Core tip: Recent evidence supports that young-onset colorectal cancer (CRC) is a “heterogeneous disease”. Newly recognized molecular alterations implicated in tumor progression, appear to contribute to its heterogeneity. Young-onset CRCs are remarkably different compared to late onset CRCs. These differences are highlighted by distinctive histologic features, site of tumor location, stage at presentation, and molecular profile. These differences support the possibility that young-onset CRC may be a different entity than late-onset CRCs. Understanding the molecular mechanisms underlying the development of young-onset CRC, will ultimately help individualize screening strategies and management for this high risk group.