Colorectal cancer (CRC) is a common and lethal disease. Both environmental and genetic factors influence the risk of developing CRC. Epidemiology CRC incidence and mortality rates vary markedly around the world. In males, CRC is the third most commonly diagnosed cancer, while it is the second for females globally. In 2012, there were 1.4 million new cases of CRC and almost 694,000 deaths. Rates are substantially higher in males than in females.
The risk of developing CRC is influenced by environmental and genetic factors. The majority of incidents of CRC are sporadic, although a familial susceptibility substantially increases the risk. The level of risk attributed to CRC risk factors are separated into two categories – risk factors that alter recommendations for CRC screening and risk factors that do not alter recommendations for CRC screening. These factors pose either a high risk or small risk, respectively. · For individuals with a personal or family history of hereditary colon cancer syndromes, adenomas with inflammatory bowel disease or exposure to abdominal radiation influence current CRC screening recommendations. Knowledge regarding the development of the CRC is rapidly evolving and this is having a positive influence of disease screening, diagnosis and management. A very high risk of developing colon cancer has been associated with several specific genetic disorders.
The most common familial colorectal cancer syndromes are Familial Adenomatous Polyposis (FAP) and Lynch Syndrome. These two conditions only explain 5% of CRC cases. Aside from these two syndromes, 10% of patients carry one or more pathogenic mutations that render them susceptible for CRC. Further, 16% of patients diagnosed with early-onset CRC (diagnosed prior to 50 years of age) may have an inherited syndrome. It has been suggested that genetic counselling and testing is a viable option for all patients to consider with early-onset CRC. Adenomatous polyposis syndromes There are three variations of familial adenomatous polyposis (FAP) – Gardner syndrome, Turcot syndrome and attenuated familial adenomatous polyposis (AFAP) – and these account for 1% of CRCs. Typically, colonic adenomas appear in childhood, with symptoms appearing usually at 16 years of age. In 90% of untreated individuals, colonic cancers occur by 45 years of age. Mutation of the adenomatous polyposis coli (APC) on chromosome 5 is responsible for FAP. Despite a different APC gene mutation, the same gene is involving in AFAP.