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- Colon cancer
- rectal cancer
- tumour location
- personalised medicine
- colorectal carcinoma
- 2,4,6-trinitrobenzene sulphonic acid
- cancer prevention
- cancer epidemiology
- non-steroidal anti-inflammatory drugs
- colorectal pathology
- colorectal cancer
Colorectal cancer comprises a heterogeneous group of diseases that arise through varying molecular carcinogenic pathways, involving complex interactions between tumour cells and the host microenvironment.1 2 It has long been appreciated that developmental and physiological differences exist between anatomic segments of the colorectum, and that colorectal cancers occur with distinctly different frequencies at different subsites.3 While approaches to surgical and adjuvant therapy have set rectal cancer as a separate entity, colon cancers still tend to get grouped together.
In the 1980s, epidemiological and molecular data suggested that cancers arising at different subsites may be biologically disparate, implying different cancer aetiologies or evolutions. These observations prompted the suggestion that the proximal and distal colon should be considered separately in aetiological studies, with the splenic flexure as a demarcation point.3 This dichotomisation has been propagated by subsequent clinical, translational and epidemiological studies,4–10 while evolving molecular data have galvanised and lent further support to the two-colon concept.11–14 It remains uncertain, however, whether the splenic flexure represents a genuine or arbitrary divide in the aetiological spectrum of colon cancers. Notably, our recent study,15 demonstrating that the frequencies of key tumour molecular features change gradually along the length of the colon (rather than abruptly at the splenic flexure), challenges the current two-colon paradigm. The aim of this article is to review data relevant to the current concept of distinct molecular pathogeneses for proximal versus distal colon cancers, to describe the impact of our recent findings and to discuss the implications for future research.
The evolution of the two-colon concept
There are incontrovertible differences between the ontogeny, morphology, biochemistry and physiology of the proximal and distal colon.11–14 Furthermore, gross macroscopic differences are well described between proximal and distal colorectal tumours.9 11–14 In …
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