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
    • 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)

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
• (4) Wang L, Du M, Wang K, Khandpur N, Rossato S L, Drouin-Chartier J et al. Association of ultra-processed food consumption with colorectal cancer risk among men and women: results from three prospective US cohort studies BMJ 2022; 378 :e068921 doi:10.1136/bmj-2021-068921