Colorectal cancer risk factors

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To view the risk factors of familial adenomatous polyposis (FAP), click here
To view the risk factors of hereditary nonpolyposis colorectal cancer (HNPCC), click here

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Saarah T. Alkhairy, M.D.

Overview

The causes and the risk factors for colorectal carcinoma are the same. There are both genetic and environmental factors that can increase the risk of colorectal carcinoma (CRC). Some of the genetic risk factors are familial adenomatous polyposis and hereditary non-polyposis colorectal cancer. Some environmental risk factors are personal/family history, history of inflammatory bowel disease, diet, alcohol, cigarette smoking, race, and gender.

Colorectal Cancer Risk Factors

The causes and the risk factors for colorectal carcinoma are the same. There are both genetic and environmental factors that can increase the risk of colorectal carcinoma[1]. FAP and HNPCC are the most common risk factors of CRC, but together these two conditions account for only about 5 percent of CRC[2].

The table below lists the genetic risk factors for colorectal carcinoma:

Genetic Risk Factor Description
Familial Adenomatous Polyposis (FAP) AD inheritance; other variants include Gardner's syndrome, Turcot's syndrome and attenuated adenomatous polyposis coli; caused by germlines mutations in the APC gene[3]; colonic cancer occurs in 90% of untreated individuals around 45 years
MUTYH-associated Polyposis (MAP) AR inheritance; caused by biallelic germline mutations in the base excision repair gene mutY homolog (MYH or MUTYH)
Lynch Syndrome AKA Hereditary Non-polyposis Colorectal Cancer (HNPCC) AD inheritance; caused by a defect in one of the mismatch repair genes, most commonly hMLH1, hMSH2, hMSH6, or PMS2; the mean age at initial cancer diagnosis is around 48 years[4]

The table below lists the environmental risk factors for colorectal carcinoma:

Environmental Risk Factor Description
Ulcerative Colitis The increase in risk begins about 8 to 10 years after the initial diagnosis of pancolitis and at 15 to 20 years if the colitis is limited to the left colon; by the fourth decade of disease it reaches as high as 30% in patients with pancolitis; pseudopolyps and strictures may increase the risk[5]
Crohn's Disease There is an increased risk if 1/3 or more of the colonic mucosa is involved
Abdominal Radiation Adult survivors of childhood malignancy who received abdominal radiation are at significant risk[6]
Diabetes Mellitus and Insulin Resistance Although it is not clear why but one possible explanation linking diabetes to CRC is hyperinsulinemia insulin is an important growth factor for colonic mucosal cells and stimulates colonic tumor cells[7]
Alcohol The elevated risk may be related to interference of folate absorption by alcohol and decreased folate intake[8]
Obesity It was reported that each 5 kg/m2 increase in BMI was associated with a 24 percent increased incidence of both colon and rectal cancer in men, and a 9 percent higher incidence of colon cancer in women[8]
Cigarette Smoking It was reported that the risk of developing CRC was increased among cigarette smokers compared to those who never smoked; for both incidence and mortality, the association was stronger for cancer of the rectum than the colon[9]
Uretercolic Anastomoses There is increased risk of neoplasia in close proximity to the ureteric stoma[10]
Diet Long-term consumption of red meat or processed meats, diets low in vegetables, and diets high in fats may be associated with an increased risk of CRC{[11][12]
Sedentary Lifestyle Regular exercise stimulates peristalsis, thereby decreasing transit time for carcinogenic substances in the colon[13]

References

  1. Chan AT, Giovannucci EL (2010). "Primary prevention of colorectal cancer". Gastroenterology. 138 (6): 2029–2043.e10. doi:10.1053/j.gastro.2010.01.057. PMC 2947820. PMID 20420944.
  2. Burt RW, DiSario JA, Cannon-Albright L (1995). "Genetics of colon cancer: impact of inheritance on colon cancer risk". Annu Rev Med. 46: 371–9. doi:10.1146/annurev.med.46.1.371. PMID 7598472.
  3. Mazur IA (1977). "[Synthesis of imidazopyrimidines and imidazoquinazolines with a common nitrogen atom]". Farm Zh (6): 37–41. PMID 598472.
  4. Parry S, Win AK, Parry B, Macrae FA, Gurrin LC, Church JM; et al. (2011). "Metachronous colorectal cancer risk for mismatch repair gene mutation carriers: the advantage of more extensive colon surgery". Gut. 60 (7): 950–7. doi:10.1136/gut.2010.228056. PMC 3848416. PMID 21193451.
  5. Ekbom A, Helmick C, Zack M, Adami HO (1990). "Ulcerative colitis and colorectal cancer. A population-based study". N Engl J Med. 323 (18): 1228–33. doi:10.1056/NEJM199011013231802. PMID 2215606.
  6. Henderson TO, Oeffinger KC, Whitton J, Leisenring W, Neglia J, Meadows A; et al. (2012). "Secondary gastrointestinal cancer in childhood cancer survivors: a cohort study". Ann Intern Med. 156 (11): 757–66, W-260. doi:10.7326/0003-4819-156-11-201206050-00002. PMC 3554254. PMID 22665813.
  7. Giovannucci E (1995). "Insulin and colon cancer". Cancer Causes Control. 6 (2): 164–79. PMID 7749056.
  8. 8.0 8.1 Harnack L, Jacobs DR, Nicodemus K, Lazovich D, Anderson K, Folsom AR (2002). "Relationship of folate, vitamin B-6, vitamin B-12, and methionine intake to incidence of colorectal cancers". Nutr Cancer. 43 (2): 152–8. doi:10.1207/S15327914NC432_5. PMID 12588695.
  9. Botteri E, Iodice S, Bagnardi V, Raimondi S, Lowenfels AB, Maisonneuve P (2008). "Smoking and colorectal cancer: a meta-analysis". JAMA. 300 (23): 2765–78. doi:10.1001/jama.2008.839. PMID 19088354.
  10. Stewart M, Macrae FA, Williams CB (1982). "Neoplasia and ureterosigmoidostomy: a colonoscopy survey". Br J Surg. 69 (7): 414–6. PMID 7104616.
  11. Chao A, Thun MJ, Connell CJ, McCullough ML, Jacobs EJ, Flanders WD; et al. (2005). "Meat consumption and risk of colorectal cancer". JAMA. 293 (2): 172–82. doi:10.1001/jama.293.2.172. PMID 15644544.
  12. Glade MJ (1999). "Food, nutrition, and the prevention of cancer: a global perspective. American Institute for Cancer Research/World Cancer Research Fund, American Institute for Cancer Research, 1997". Nutrition. 15 (6): 523–6. PMID 10378216.
  13. Lynch BM, Boyle T (2014). "Distinguishing sedentary from inactive: implications for meta-analyses". Br J Cancer. 111 (11): 2202–3. doi:10.1038/bjc.2014.106. PMC 4260011. PMID 24569462.


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