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Abstract
One of the most critical characteristics of colorectal cancer (CRC) is the difference between proximal (right-sided colon cancer, RCC) and distal (left-sided colon cancer, LCC) disease. The recent CRC studies showed the unique characteristics of RCC; RCCs were more prevalent in women than men and old patients, and the age difference between RCC and LCC was more apparent in women. Moreover, relatively poor protection against RCC by colonoscopy is a clearly hot issue for alarm. Thus, the left and right colon have been considered as dichotomous or even different organs in the view of molecular, histopathological, epidemiologic and clinical bases for over three decades. However, the evolutionary data suggesting linearity from the rectum to ascending colon beyond the simple right-left dichotomization in the views of cancer molecular features and site-specific clinicopathological differences, support the need for a paradigm shift to the colorectal continuum model rather than the traditional two-colon concept. This new multi-segmental or colorectal continuum hypothesis would provide both the better understanding of the complex etiology of colorectal carcinogenesis and the tailored preventive and therapeutic strategies for CRC including individualized CRC screening programs.
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Fig. 1.
Integrative analysis of genomic changes according to the site of colon in 195 CRCs. Hypermutated cancers have near-diploid genomes and are highly enriched for hypermethylation, CIMP phenotype and BRAF (V600E) mutations. Non-hypermutated tumours originating from different sites are virtually indistinguishable from each other on the basis of their copy-number alteration patterns, DNA methylation or gene-expression patterns (citing Fig. 2 in the article of the Cancer Genome Atlas Network [Nature 2012;487:330–337]38 with the original author's permission). CIMP, CpG island methylator phenotype; H, high; L, low; MSI, microsatellite instability; CIN, chromosomal instability.
Fig. 2.
Schematic illustration of the differences between the two-colon concept and the continuum model. The molecular characteristics including a high degree of CpG island methylator phenotype (CIMP-high), a high degree of microsatellite instability (MSI-high) and BRAF mutation increase linearly from the rectum to the ascending colon according to the new continuum model. Data from numerous previous two-colon studies appear to support the two-colon concept (left, top), even when it is likely that a continuum exists for the measured marker along the proximal- distal axis of the colon (left, bottom). The design of two-colon studies does not permit adequate evaluation of the linearity of marker frequency by colon subsite (modified from Fig. 1 in the article of Yamauchi et al. [Gut 2012; 61:847–854]16 with the original author's permission).
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