aetiology and risk factors

Last edited 10/2022 and last reviewed 10/2022

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
      • association between consumption of ultra-processed foods and risk of colorectal cancer:
        • a study found that high consumption of total ultra-processed foods in men and certain subgroups of ultra-processed foods in men and women was associated with an increased risk of colorectal cancer (4):
          • compared with those in the lowest fifth of ultra-processed food consumption, men in the highest fifth of consumption had a 29% higher risk of developing colorectal cancer and the positive association was limited to distal colon cancer (72% increased risk)
            • associations remained significant after further adjustment for body mass index or indicators of nutritional quality of the diet (that is, western dietary pattern or dietary quality score).
            • no association was observed between overall ultra-processed food consumption and risk of colorectal cancer among women
            • among subgroups of ultra-processed foods, higher consumption of meat/poultry/seafood based ready-to-eat products among men and ready-to-eat/heat mixed dishes among women was associated with increased risk of colorectal cancer
            • yogurt and dairy based desserts were negatively associated with the risk of colorectal cancer among women
    • 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)


  • 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%