Colon Cancer: A Civilization Disorder

Abstract

Colorectal cancer arises in individuals with acquired or inherited genetic predisposition who are exposed to a range of risk factors. Many of these risk factors are associated with affluent Western societies. More than 95% of colorectal cancers are sporadic, arising in individuals without a significant hereditary risk. Geographic variation in the incidence of colorectal cancer is considerable with a higher incidence observed in the West. Environmental factors contribute substantially to this variation. A number of these risk factors are associated with a Western lifestyle and could be considered a product of ‘civilization’. Recently, smoking has been recognized as a risk factor. Energy consumption also influences colorectal cancer risk, with obesity increasing risk and exercise reducing risk. However, the strongest contribution to environmental risk for colorectal cancer is dietary. Consumption of fat, alcohol and red meat is associated with an increased risk. Fresh fruit and vegetables and dietary fibre may be protective. Much has been learnt recently about the molecular pathogenesis of colorectal cancer. Colorectal cancer always arises in the context of genomic instability. There is inactivation of the tumour suppressor genes adenomatous polyposis coli, p53, transforming growth factor-β, activation of oncogene pathways including K-ras, and activation of the cyclooxygenase-2, epidermal growth factor receptor and vascular endothelial growth factor pathways. The mechanisms by which some environmental factors modify the mutation risk in these pathways have been described.

Epidemiology of colorectal cancer in Turkey: A cross-sectional disease registry study (A Turkish Oncology Group trial)

“…In the previous studies; age, obesity, diabetes mellitus, family history, hereditary conditions, inflammatory bowel disease, diet (consumption of red and processed meat, diet low in fruits and vegetable), and lifestyle factors (physical activity, alcohol in-take, and smoking) were positively correlated with the risk of colorectal cancers (7,13,(15)(16)(17). It was also reported that longterm ulcerative colitis and Crohn's disease increases the risk of developing colorectal cancer (18,19).…”

Mechanisms Linking Colorectal Cancer to the Consumption of (Processed) Red Meat: A Review

“…Approximately 5% of all CRC cases are due to inherited genetic mutations, including many syndromes such as Familial Adenomatous Polyposis and Lynch syndrome (Power et al, 2010;Al-Sohaily et al, 2012); however, the vast majority of CRC cases have been linked to environmental causes rather than to heritable genetic changes (Lund et al, 2011;Watson and Collins, 2011). For many years, diet is recognized as an important factor in disease etiology and risk of CRC (Modan, 1977), including the consumption of red and processed red meat.…”

Effects of Dietary Counseling on Patients with Colorectal Cancer

“…The inheritance determines individual susceptibility to sporadic cancer but the lifestyle and environmental exposures are necessary for cancer expression. Colorectal cancer incidence varies between different geographic regions and incidence and mortality rates have been highest in developed western nations (10,11). The basic argument that environment plays a huge role in colorectal cancer expression we get from observational studies in migrant populations.…”

“…Migrants from low-incident regions to the high-incident regions of North America within one generation accept the incidence of the host country. Yet, studies with migrants also suggest that geographic variation in colorectal cancer incidences is due to environmental exposures and not due to the inherent predisposition (racial and ethnic group) (1,10,11). Population based investigations have found many dietary and other environmental factors associated with colorectal cancer incidence (2).…”