Colorectal cancer causes
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To view the causes of familial adenomatous polyposis (FAP), click here
To view the causes 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 causes of colorectal carcinoma (CRC). Some of the genetic causes are familial adenomatous polyposis and hereditary non-polyposis colorectal cancer. Some environmental causes are personal/family history, history of inflammatory bowel disease, diet, alcohol, cigarette smoking, and abdominal radiation.
Colorectal Cancer Risk Factors
The causes and the risk factors for colorectal carcinoma are the same. There are both genetic and environmental causes of colorectal carcinoma[1]. FAP and HNPCC are the most common causes of CRC, but together these two conditions account for only about 5 percent of CRC[2].
The table below lists the genetic causes for colorectal carcinoma:
| Genetic Cause | 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 causes for colorectal carcinoma:
| Environmental Cause | Description |
| Family History | There is a risk if there is a single affected first-degree relative with CRC; the risk further increases if two first-degree relatives have CRC or the diagnosis was below ages 50-60 years; may have increased risk if a first-degree family member has an adenomatous colonic polyp[5] |
| Personal History | There is a risk if there is a history of CRC or adenomatous polyps, particularly if they are multiple polyps >1 cm, or if the polyps are villous/tubulovillous[6] |
| 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[7] |
| Crohn's Disease | There is an increased risk if 1/3 or more of the colonic mucosa is involved |
| Age | The risk of developing CRC increases with age; most cases occur in the 60s and 70s, while cases before age 50 are uncommon unless a family history of early colon cancer is present, cancer in african american individuals tends to occur earlier[8] |
| Abdominal Radiation | Adult survivors of childhood malignancy who received abdominal radiation are at significant risk[9] |
| Race | The African American race has the highest CRC race of all the ethnic groups; the mortality in is 20% higher in the African American race compared to the Caucasian race[10] |
| Gender | CRC mortality is about 25 percent higher in men than in women [11] |
| Acromegaly | Patients with acromegaly are more likely to have multiple adenomatous polyps[12] |
| Renal Transplantation | Renal transplantation, associated with long-term immunosuppression, has been linked with increased CRC risk[13] |
| 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[14] |
| Alcohol | The elevated risk may be related to interference of folate absorption by alcohol and decreased folate intake[15] |
| 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[15] |
| 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[16] |
| Uretercolic Anastomoses | There is increased risk of neoplasia in close proximity to the ureteric stoma[17] |
| 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{[18][19] |
| Coronary Heart Disease | The presence of coronary heart disease has been associated with an increased risk of CRC{[20] |
| Sedentary Lifestyle | Regular exercise stimulates peristalsis, thereby decreasing transit time for carcinogenic substances in the colon[21] |
| Other cancers | Ovarian, endometrial, and breast cancer; there is an increase in risk is more likely if the first primary is diagnosed at an early age[22] |
References
- ↑ 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.
- ↑ 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.
- ↑ Mazur IA (1977). "[Synthesis of imidazopyrimidines and imidazoquinazolines with a common nitrogen atom]". Farm Zh (6): 37–41. PMID 598472.
- ↑ 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.
- ↑ Winawer SJ, Zauber AG, Gerdes H, O'Brien MJ, Gottlieb LS, Sternberg SS; et al. (1996). "Risk of colorectal cancer in the families of patients with adenomatous polyps. National Polyp Study Workgroup". N Engl J Med. 334 (2): 82–7. doi:10.1056/NEJM199601113340204. PMID 8531963.
- ↑ Atkin WS, Morson BC, Cuzick J (1992). "Long-term risk of colorectal cancer after excision of rectosigmoid adenomas". N Engl J Med. 326 (10): 658–62. doi:10.1056/NEJM199203053261002. PMID 1736104.
- ↑ 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.
- ↑ Agrawal S, Bhupinderjit A, Bhutani MS, Boardman L, Nguyen C, Romero Y; et al. (2005). "Colorectal cancer in African Americans". Am J Gastroenterol. 100 (3): 515–23, discussion 514. doi:10.1111/j.1572-0241.2005.41829.x. PMID 15743345.
- ↑ 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.
- ↑ Jemal A, Siegel R, Xu J, Ward E (2010). "Cancer statistics, 2010". CA Cancer J Clin. 60 (5): 277–300. doi:10.3322/caac.20073. PMID 20610543.
- ↑ Schoenfeld, Philip; Cash, Brooks; Flood, Andrew; Dobhan, Richard; Eastone, John; Coyle, Walter; Kikendall, James W.; Kim, Hyungjin Myra; Weiss, David G.; Emory, Theresa; Schatzkin, Arthur; Lieberman, David (2005). "Colonoscopic Screening of Average-Risk Women for Colorectal Neoplasia". New England Journal of Medicine. 352 (20): 2061–2068. doi:10.1056/NEJMoa042990. ISSN 0028-4793.
- ↑ Delhougne B, Deneux C, Abs R, Chanson P, Fierens H, Laurent-Puig P; et al. (1995). "The prevalence of colonic polyps in acromegaly: a colonoscopic and pathological study in 103 patients". J Clin Endocrinol Metab. 80 (11): 3223–6. doi:10.1210/jcem.80.11.7593429. PMID 7593429.
- ↑ Park JM, Choi MG, Kim SW, Chung IS, Yang CW, Kim YS; et al. (2010). "Increased incidence of colorectal malignancies in renal transplant recipients: a case control study". Am J Transplant. 10 (9): 2043–50. doi:10.1111/j.1600-6143.2010.03231.x. PMID 20883538.
- ↑ Giovannucci E (1995). "Insulin and colon cancer". Cancer Causes Control. 6 (2): 164–79. PMID 7749056.
- ↑ 15.0 15.1 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.
- ↑ 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.
- ↑ Stewart M, Macrae FA, Williams CB (1982). "Neoplasia and ureterosigmoidostomy: a colonoscopy survey". Br J Surg. 69 (7): 414–6. PMID 7104616.
- ↑ 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.
- ↑ 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.
- ↑ Chan AO, Jim MH, Lam KF, Morris JS, Siu DC, Tong T; et al. (2007). "Prevalence of colorectal neoplasm among patients with newly diagnosed coronary artery disease". JAMA. 298 (12): 1412–9. doi:10.1001/jama.298.12.1412. PMID 17895457.
- ↑ 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.
- ↑ Evans HS, Møller H, Robinson D, Lewis CM, Bell CM, Hodgson SV (2002). "The risk of subsequent primary cancers after colorectal cancer in southeast England". Gut. 50 (5): 647–52. PMC 1773208. PMID 11950810.