Molecular Determinants of Colon Cancer Susceptibility in the East and West

Abstract

The currently available knowledge of factors that dictate the development and progression as well as the clinical outcome of colorectal cancers (CRC) is mainly derived from Western countries. Considerable number of publications document different incidence rates and contrasting clinical features of CRC in various groups such as the differences between urban vs. rural areas, young vs. old age and the East vs. the West. In particular, Egyptian CRC is a surprisingly young age disease with higher proportion of poorly differentiated and advanced stage cancers as compared to the Western counterparts. Less number of publications addressed the molecular genetics and epigenetic basis of these differences. The available data on CRC and other cancers support a substantial role of several environmental risk factors which impinge on the epigenome and alter the overall cellular and tissue homeostasis. Thus, environmental factors could play a role in predisposition to CRC in general as well as in shaping distinct disease phenotypes in different settings. On the other hand, the environment offers a wide range of preventive modalities including a selection of dietary chemopreventive agents which could play a significant role in fighting cancer at early stages. We here compare the clinical and molecular characteristics of Eastern and Western CRC based on the latest literature. The genetic, epigenetic and environmental etiologies for the observed differences are discussed. Finally, prospects for cancer prevention in light of the increased etiologic understanding are outlined.

Keywords: Carcinogens; colon cancer; dietary chemoprevention; environment; epigenetics; ethnic variation.