Unpacking the essentials of genetic basis of colorectal cancer. A bird's eye view for the trainee.: Review Article

Abstract

Background: Ever since Bert Vogelstein’s landmark paper on “clonal analysis of human colorectal
tumours”, a seismic body of information has been added for anyone searching for the basics to
grapple with. Colorectal cancer management now incorporates molecular studies to determine
responses to treatment, prognostication, and identification of hereditary cancers and institute
effective surveillance programs. This review aims to answer a few basic questions (1) are there
pathways in addition to the adenoma-carcinoma sequence? (2) what are the genetic mechanisms
underlying the morphological pathways? (3) how do the classical inherited CRC syndromes fit
into the above pathways? And (4) what are the benefits of understanding the molecular basis
of colorectal cancers? The two main theories regarding the morphological origins of colorectal
cancer are the adenoma-carcinoma sequence and the De-novo origins. The underlying genetic
models are the (i) chromosomal instability pathway (CIN), (ii) the microsatellite instability pathway
(MSI), and (iii) the CpG Island methylator phenotype (CIMP) pathways. Though unique, the
pathways communicate with each other. Hereditary Non-Polyposis Colic (HNPCC) and Familial
Adenomatous Polyposis (FAP) the two commonest inherited cancer syndromes show differences
in their genetic makeup and behaviour but share the adenoma-carcinoma pathway.

Conclusion: We have moved a long way to improve management by administering tailored
treatment based on the genetic profile of colorectal cancer. Therefore, understanding the genetic
basis and the main pathways are essential for those in gastrointestinal subspecialties. The review
has been made especially with the trainee gastrointestinal surgeon in mind to reiterate the basics