Colorectal cancer, one entity or three

Abstract

Abstract:Understanding of the mechanism of colorectal carcinogenesis has been gaining momentum for some years on account of its high incidence and impact on the lives of individuals affected. Different genetic abnormalities have been found in colorectal cancers from different sites. For example, proximal colon cancer is usually related to the nucleotide instability pathway, as microsatellite instability (MSI). However, distal colon cancer is usually associated with specific chromosomal instability (CIN). The development of cancer at the rectum, though similar to that at the colon, displays its own unique features. These differences might be partially attributed to different embryological development and physiological circumstances. Environmental factors such as diet and alcohol intake also differ in their role in the development of tumors in the three segments, proximal colon, distal colon, and rectum. "Proximal shift" of colon cancer has been known for some time, and survival rates of colorectal cancer are higher when rectal cancers are excluded, both of which emphasize the three different segments of colorectal cancer and their different properties. Meanwhile, colonic and rectal cancers are distinctive therapeutic entities. The concept of three entities of colorectal cancer may be important in designing clinical trails or therapeutic strategies. However, the dispute about the inconsistency of data concerning the site-specific mechanism of colorectal carcinoma does exist, and more evidence about molecular events of carcinogenesis and targeted therapy needs to be collected to definitely confirm the conception.

Characterization of rectal, proximal and distal colon cancers based on clinicopathological, molecular and protein profiles

“…Recent epidemiologic studies have reported a proximal migration of CRCs evidenced by increased incidence of right-sided colon cancers and a decrease in incidence of rectosigmoid tumors (2,3), suggestive of different risk factors associated with carcinogenesis in proximal and distal colon (4,5). These data support the concept originally proposed by Bufill in 1990 that cancers originating from these two different anatomical locations should have distinct molecular pathogenesis (6).…”

Expression of programmed cell death protein 1 (PD-1) and its ligand PD-L1 in colorectal cancer: Relationship with sidedness and prognosis

“…However, rectal cancer differs from descending and sigmoid colon cancer in molecular features, treatment approaches, and prognosis. 50 , 51 Thus, we believe that it is more appropriate to apply the herein used definition on future studies.…”

Plasma and dietary carotenoids and vitamins A, C and E and risk of colon and rectal cancer in the European Prospective Investigation into Cancer and Nutrition

“…However, etiological pathways underlying colon cancers proximal to the splenic flexure are different from those distal to the splenic flexure and evidence that risk factors for tumors originating from different colorectal subsites vary is accumulating. 14,15 The aim of this study was to assess the association of prediagnostic plasma concentrations and dietary intakes of carotenoids and vitamins A, C and E with the risk of colon and rectal cancer in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. In addition, analyses for colon cancer were stratified by subsite.…”