Left-sided primary colon tumors are associated with significantly lower mortality than right-sided tumors, according to a systematic review and meta-analysis published online Oct. 27 in JAMA Oncology.

Previous research has suggested that left- and right-sided colon cancer have different biological, molecular, and clinical features, wrote Fausto Petrelli, MD, from the oncology department at ASST Bergamo Ovest (Italy) and his coauthors.

Right-sided colon cancers have a higher prevalence of iron-deficiency anemia because of occult blood loss and are associated with defective mismatch repair genes and KRAS and BRAF mutations. Left-sided colon cancer is associated with a greater incidence of hematochezia and altered bowel habits, and is linked more commonly to the chromosomal instability pathway, p53, NRAS, microRNA-146a, microRNA-147b, and microRNA-1288 (JAMA Oncology. 2016 Oct 27. doi: 10.1001/jamaoncol.2016.4227).

A meta-analysis of 66 studies involving 1,437,846 patients, in which the cancer side was reported and survival data was available, showed patients with a left-sided primary tumor had a significant 18% lower risk of death (P less than .001), compared with those with right-side tumors. This relationship was independent of other factors including stage, race, adjuvant chemotherapy, and the quality of the study, although studies that only included patients with stage IV disease showed an even greater 27% reduction in death in those with left-side tumors.

“An increasingly large amount of evidence is accumulating showing that colon tumors proximal and distal to the splenic flexure are distinct clinical and biological entities,” the authors wrote. “Apart from having a different embryological origin – proximal colon from midgut and distal colon and rectum from hindgut – the right colon displays peculiar differences in mucosal immunology, probably owing to differences in gut microbiota.”

For example, the proximal colon has been found to have a higher concentration of eosinophils and intraepithelial T cells, which may be due to the fact that immune cells in the distal colorectum have to walk an even finer line between immunogenicity against pathogens and tolerance for normal gut microbiota.

“This observation could also explain the differences in immunological response to tumors developing in the proximal colon characterized by an increased immune activity and, in turn, reflect the specific differences in pathogenesis and outcome.”

Given their findings, the authors argued that side of origin should be included as a prognostic factor for both early and advanced disease, and should also be considered in treatment decision making and in future clinical trials.

No conflicts of interest were declared.


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