aetiology and risk factors

Majority of colorectal cancers arises sporadically (1)

• colorectal cancer most commonly occurs sporadically and is inherited in only 5%-10% of cases (2)

Risks factors for colorectal carcinoma include:

• increasing age
  • 83% of cases are seen in people who are 60 years or older
• male sex
• environmental factors
  • dietary factors e.g. - red meat and processed meat, high-fat diet, inadequate intake of fibre
• obesity
• 10% of colon cancers in the UK are related to obesity
• is associated with colonic adenomata but not with carcinoma
• sedentary lifestyle
• high levels of physical activity reduce the risk of colorectal carcinoma
• diabetes mellitus
• smoking
  • consistently been associated with large colorectal adenomas, which are generally accepted as precursors for cancer
  • evidence suggests a temporal pattern consistent with an induction period of three to four decades between genotoxic exposure and the diagnosis of colorectal cancer
    • in the USA one in five colorectal cancers may be potentially attributable to tobacco use (2)
• high alcohol consumption (1)
  
  
• hormone replacement therapy:
• most studies show that hormone replacement therapy in women reduces the chance of colorectal cancer
• there is evidence that postmenopausal oestrogen plus progesterone hormone use decreases the incidence of colorectal tumour but a non-comparable benefit was demonstrated for oestrogen alone (2)
  
  
• genetic factors:
• familial adenomatous polyposis
• Gardner's and Turcot's syndromes
• familial colorectal cancer syndrome (Lynch I)
• hereditary adenocarcinomatosis syndrome (Lynch II)
• family history of colorectal carcinoma
  
  
• colorectal disease:
• inflammatory bowel disease
• benign colorectal polyps
• previous history of colonic polyps or colorectal cancer
• pelvic irradiation

• metabolic syndrome (high blood pressure, increased waist circumference, hypertriglyceridaemia, low levels of high-density lipoprotein cholesterol or diabetes/hyperglycaemia)
  • there is a modest, positive association with colorectal cancer incidence among men, but not among women and there was a clear relationship with the number of components present (2)

Notes:

• genetic vulnerability to colon cancer has been attributed to either polyposis or non-polyposis syndromes (2)
  • main syndrome of the first group is the familial adenomatous polyposis (FAP), which is associated with mutation or loss of FAP (also called the adenomatous polyposis coli-APC) gene
  • hereditary non-polyposis colorectal cancer (HNPCC) syndrome is associated with germ-line mutations in six DNA mismatch repair genes
    • cumulative incidence of HNPCC-related cancers was determined in gene carriers in the Finnish Cancer Registry: by age 70 years, the percentage developing colorectal cancers was 82%

Reference:

• (1) Cunningham D et al. Colorectal cancer. Lancet. 2010;375(9719):1030-47
• (2) Labianca R et al. Primary colon cancer: ESMO Clinical Practice Guidelines for diagnosis, adjuvant treatment and follow-up. Ann Oncol. 2010;21 Suppl 5:v70-7. 
• (3) National Institute for Health and Clinical Excellence (NICE) 2014. Colorectal cancer: the diagnosis and management of colorectal cancer

Last reviewed 07/2021