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World J Gastroenterol. Dec 28, 2014; 20(48): 18151-18164
Published online Dec 28, 2014. doi: 10.3748/wjg.v20.i48.18151
Colorectal carcinogenesis-update and perspectives
Hans Raskov, Hans-Christian Pommergaard, Jakob Burcharth, Jacob Rosenberg
Hans Raskov, Speciallægecentret ved Diakonissestiftelsen, 2000 Frederiksberg, Denmark
Hans-Christian Pommergaard, Jakob Burcharth, Jacob Rosenberg, Department of Surgery, Herlev Hospital, University of Copenhagen, DK-2730 Herlev, Denmark
Author contributions: All authors contributed to conception and design, critical revision and final approval of the manuscript; and Raskov H wrote the first draft.
Correspondence to: Dr. Hans Raskov, Speciallægecentret ved Diakonissestiftelsen, Peter Bangs vej 3, 2000 Frederiksberg, Denmark.
Telephone: +45-38-868222 Fax: +45-38-868222
Received: June 28, 2014
Revised: August 18, 2014
Accepted: September 29, 2014
Published online: December 28, 2014

Colorectal cancer (CRC) is a very common malignancy in the Western World and despite advances in surgery, chemotherapy and screening, it is still the second leading cause of cancer deaths in this part of the world. Numerous factors are found important in the development of CRC including colonocyte metbolism, high risk luminal environment, inflammation, as well as lifestyle factors such as diet, tobacco, and alchohol consumption. In recent years focus has turned towards the genetics and molecular biology of CRC and several interesting and promising correlations and pathways have been discovered. The major genetic pathways of CRC are the Chromosome Instability Pathway representing the pathway of sporadic CRC through the K-ras, APC, and P53 mutations, and the Microsatellite Instability Pathway representing the pathway of hereditary non-polyposis colon cancer through mutations in mismatch repair genes. To identify early cancers, screening programs have been initiated, and the leading strategy has been the use of faecal occult blood testing followed by colonoscopy in positive cases. Regarding the treatment of colorectal cancer, significant advances have been made in the recent decade. The molecular targets of CRC include at least two important cell surface receptors: the epidermal growth factor receptor and the vascular endothelial growth factor receptor. The genetic and molecular knowledge of CRC has widen the scientific and clinical perspectives of diagnosing and treatment. However, despite significant advances in the understanding and treatment of CRC, results from targeted therapy are still not convincing. Future studies will determine the role for this new treatment modality.

Keywords: Colorectal carcinogenesis, Risk factors, Microbiology, Genetics, Diet, Microbiome, Inflammation

Core tip: Over the last years the treatment of colorectal cancer has become increasingly dependent on individual patient profiling with regard to both microbiology and genetics. Apart from lifestyle factors and age, genetic predisposition, inflammation and impact of the microbiome appear to be important contributors to malignant transformation in the colon. The review gives an update on colorectal carcinogenesis.