Colorectal Cancer Genetics, Incidence and Risk Factors: In Search for Targeted Therapies

Rodney Hull,1 Flavia Zita Francies,1 Meryl Oyomno,2 Zodwa Dlamini1,3 1SAMRC/UP Precision Prevention & Novel Drug Targets for HIV-Associated Cancers (PPNDTHAC) Extramural Unit, Pan African Cancer Research Institute (PACRI), University of Pretoria, Faculty of Health Sciences, Hatfield 0028, South Africa; 2Department of Surgery, Faculty of Health Sciences, Steve Biko Academic Hospital and the University of Pretoria, Pretoria 0007, South Africa; 3Faculty of Health Sciences, School of Clinical Medicine, University of the Witwatersrand, Parktown 2193, South AfricaCorrespondence: Zodwa DlaminiSA-MRC/UP Precision Prevention & Novel Drug Targets for HIV-Associated Cancers (PPNDTHAC) Extramural Unit, Pan African Cancer Research Institute (PACRI), University of Pretoria, Faculty of Health Sciences, Room 4.35 Pathology Building, Hatfield 0028, South AfricaTel +27 761474878Email Zodwa.Dlamini@up.ac.zaAbstract: Each year, colorectal cancers (CRCs) affect over a quarter of a million people. The risk of developing CRC in industrialized nations is approximately 5%. When the disease is localised, treatment success rates range from 70– 90%; however, advanced CRC has a high mortality rate, consistently ranking in the top three causes of cancer-related deaths. There is a large geographic difference in global distribution, and CRC is predominantly associated with developed countries and a Western lifestyle and diet. As such, the developed world accounts for more than 63% of all cases of CRC. Geographic variations also predict cancer outcomes, which differ between racial and ethnic groups. This variation is due to inequalities in wealth, differences in the exposure to risk factors and barriers to high-quality cancer prevention, early detection and treatment. The aim of this paper was to review CRC in low- and middle-income countries such as South Africa, India, Brazil and China, and compare them with high-income countries such as the United States of America and the United Kingdom. It is important to note that these economically less developed countries, with historically low CRC rates, are experiencing an increased frequency of CRC. The review also discusses biological markers and genetic pathways involved in the development of colorectal cancer. Genes known to be responsible for the most common forms of inherited CRCs have also been identified but more remain to be identified. This would provide more candidate genes to be added to known biomarkers. CRC burden can be controlled through the widespread application of existing knowledge, such as reduced smoking habits, vaccination, early detection and promoting physical activity, accompanied by a healthy diet. An increased understanding of the molecular mechanisms and events underlying colorectal carcinogenesis will enable the development of new targets and therapeutic drugs.Keywords: colorectal cancer, WNT signaling pathway, RAS pathway, alcohol consumption, physical activity