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| To view the causes of familial adenomatous polyposis (FAP), click [[Familial adenomatous polyposis causes|'''here''']]<br> | | To view the causes of familial adenomatous polyposis (FAP), click [[Familial adenomatous polyposis causes|'''here''']]<br> |
| To view the causes of hereditary nonpolyposis colorectal cancer (HNPCC), click [[Hereditary nonpolyposis colorectal cancer causes|'''here''']]<br><br> | | To view the causes of hereditary nonpolyposis colorectal cancer (HNPCC), click [[Hereditary nonpolyposis colorectal cancer causes|'''here''']]<br><br> |
| {{CMG}} {{AE}} Saarah T. Alkhairy, M.D. | | {{CMG}} {{AE}}; {{RAK}} Saarah T. Alkhairy, M.D. |
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| ==Overview== | | ==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. | | The cause of colorectal cancer has not been identified. To review risk factors for the development of colorectal cancer, [[Colorectal cancer risk factors|click here]]. |
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| ==Colorectal Cancer Risk Factors== | | ==Colorectal Cancer Causes== |
| The causes and the risk factors for colorectal carcinoma are similar. There are both genetic and environmental causes of colorectal carcinoma<ref name="pmid20420944">{{cite journal| author=Chan AT, Giovannucci EL| title=Primary prevention of colorectal cancer. | journal=Gastroenterology | year= 2010 | volume= 138 | issue= 6 | pages= 2029-2043.e10 |pmid=20420944 | doi=10.1053/j.gastro.2010.01.057 | pmc=PMC2947820 |url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20420944 }}</ref>. FAP and HNPCC are the most common causes of CRC, but together these two conditions account for only about 5 percent of CRC<ref name="pmid7598472">{{cite journal| author=Burt RW, DiSario JA, Cannon-Albright L| title=Genetics of colon cancer: impact of inheritance on colon cancer risk. | journal=Annu Rev Med | year= 1995 | volume= 46 |issue= | pages= 371-9 | pmid=7598472 | doi=10.1146/annurev.med.46.1.371 | pmc= |url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7598472 }} </ref>. | | The cause of colorectal cancer has not been identified. However, there are certain risk factors that predisposes to risk of CRC. |
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| The table below lists the genetic causes for colorectal carcinoma:
| | To review risk factors for the development of colorectal cancer, [[Colorectal cancer risk factors|click here]]. |
| {| {{table}}
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| | align="center" style="background:#f0f0f0;"|'''Genetic Cause'''
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| | align="center" style="background:#f0f0f0;"|'''Description'''
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| | '''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<ref name="pmid598472">{{cite journal| author=Mazur IA| title=[Synthesis of imidazopyrimidines and imidazoquinazolines with a common nitrogen atom]. | journal=Farm Zh | year= 1977 | volume= | issue= 6 |pages= 37-41 | pmid=598472 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=598472}}</ref>; colonic cancer occurs in 90% of untreated individuals around 45 years
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| | '''MUTYH-associated Polyposis (MAP)'''||AR inheritance; caused by biallelic germline [[mutations]] in the base excision repair gene mutY homolog (MYH or MUTYH)
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| | '''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<ref name="pmid21193451">{{cite journal| author=Parry S, Win AK, Parry B, Macrae FA, Gurrin LC, Church JM et al.| title=Metachronous colorectal cancer risk for mismatch repair gene mutation carriers: the advantage of more extensive colon surgery. | journal=Gut | year= 2011 | volume= 60 | issue= 7 | pages= 950-7 | pmid=21193451 | doi=10.1136/gut.2010.228056 | pmc=PMC3848416 |url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21193451 }}</ref>
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| The table below lists the environmental causes for colorectal carcinoma:
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| | align="center" style="background:#f0f0f0;"|'''Environmental Cause'''
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| | align="center" style="background:#f0f0f0;"|'''Description'''
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| | '''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<ref name="pmid8531963">{{cite journal| author=Winawer SJ, Zauber AG, Gerdes H, O'Brien MJ, Gottlieb LS, Sternberg SS et al.| title=Risk of colorectal cancer in the families of patients with adenomatous polyps. National Polyp Study Workgroup. | journal=N Engl J Med | year= 1996 | volume= 334 | issue= 2 | pages= 82-7 | pmid=8531963 | doi=10.1056/NEJM199601113340204 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8531963 }} </ref>
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| | '''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<ref name="pmid1736104">{{cite journal| author=Atkin WS, Morson BC, Cuzick J| title=Long-term risk of colorectal cancer after excision of rectosigmoid adenomas. | journal=N Engl J Med | year= 1992 | volume= 326 | issue= 10 | pages= 658-62 | pmid=1736104 | doi=10.1056/NEJM199203053261002 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1736104 }} </ref>
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| | '''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<ref name="pmid2215606">{{cite journal| author=Ekbom A, Helmick C, Zack M, Adami HO| title=Ulcerative colitis and colorectal cancer. A population-based study. | journal=N Engl J Med | year= 1990 | volume= 323 | issue= 18 | pages= 1228-33 | pmid=2215606 | doi=10.1056/NEJM199011013231802 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2215606 }} </ref>
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| | '''Crohn's Disease'''||There is an increased risk if 1/3 or more of the colonic mucosa is involved
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| | '''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<ref name="pmid15743345">{{cite journal| author=Agrawal S, Bhupinderjit A, Bhutani MS, Boardman L, Nguyen C, Romero Y et al.| title=Colorectal cancer in African Americans. | journal=Am J Gastroenterol | year= 2005 | volume= 100 | issue= 3 | pages= 515-23; discussion 514 | pmid=15743345 | doi=10.1111/j.1572-0241.2005.41829.x | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15743345 }} </ref>
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| | '''Abdominal Radiation'''||Adult survivors of childhood malignancy who received [[abdominal]] radiation are at significant risk<ref name="pmid22665813">{{cite journal| author=Henderson TO, Oeffinger KC, Whitton J, Leisenring W, Neglia J, Meadows A et al.| title=Secondary gastrointestinal cancer in childhood cancer survivors: a cohort study. | journal=Ann Intern Med | year= 2012 | volume= 156 | issue= 11 | pages= 757-66, W-260 | pmid=22665813 | doi=10.7326/0003-4819-156-11-201206050-00002 | pmc=PMC3554254 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22665813 }} </ref>
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| | '''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<ref name="pmid20610543">{{cite journal| author=Jemal A, Siegel R, Xu J, Ward E| title=Cancer statistics, 2010. | journal=CA Cancer J Clin | year= 2010 | volume= 60 | issue= 5 | pages= 277-300 | pmid=20610543 | doi=10.3322/caac.20073 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20610543 }} </ref>
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| | '''Gender'''||CRC mortality is about 25 percent higher in men than in women <ref name="SchoenfeldCash2005">{{cite journal|last1=Schoenfeld|first1=Philip|last2=Cash|first2=Brooks|last3=Flood|first3=Andrew|last4=Dobhan|first4=Richard|last5=Eastone|first5=John|last6=Coyle|first6=Walter|last7=Kikendall|first7=James W.|last8=Kim|first8=Hyungjin Myra|last9=Weiss|first9=David G.|last10=Emory|first10=Theresa|last11=Schatzkin|first11=Arthur|last12=Lieberman|first12=David|title=Colonoscopic Screening of Average-Risk Women for Colorectal Neoplasia|journal=New England Journal of Medicine|volume=352|issue=20|year=2005|pages=2061–2068|issn=0028-4793|doi=10.1056/NEJMoa042990}}</ref>
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| | '''Acromegaly'''||Patients with acromegaly are more likely to have multiple adenomatous [[polyps]]<ref name="pmid7593429">{{cite journal| author=Delhougne B, Deneux C, Abs R, Chanson P, Fierens H, Laurent-Puig P et al.| title=The prevalence of colonic polyps in acromegaly: a colonoscopic and pathological study in 103 patients. | journal=J Clin Endocrinol Metab | year= 1995 | volume= 80 | issue= 11 | pages= 3223-6 | pmid=7593429 | doi=10.1210/jcem.80.11.7593429 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7593429}} </ref>
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| | '''Renal Transplantation'''||Renal transplantation, associated with long-term immunosuppression, has been linked with increased CRC risk<ref name="pmid20883538">{{cite journal| author=Park JM, Choi MG, Kim SW, Chung IS, Yang CW, Kim YS et al.| title=Increased incidence of colorectal malignancies in renal transplant recipients: a case control study. | journal=Am J Transplant | year= 2010 | volume= 10 | issue= 9 | pages= 2043-50 | pmid=20883538 | doi=10.1111/j.1600-6143.2010.03231.x | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20883538 }} </ref>
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| | '''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<ref name="pmid7749056">{{cite journal| author=Giovannucci E| title=Insulin and colon cancer. | journal=Cancer Causes Control | year= 1995 | volume= 6 | issue= 2 | pages= 164-79 | pmid=7749056 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7749056 }} </ref>
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| | '''Alcohol'''||The elevated risk may be related to interference of [[folate]] absorption by [[alcohol]] and decreased folate intake<ref name="pmid12588695">{{cite journal| author=Harnack L, Jacobs DR, Nicodemus K, Lazovich D, Anderson K, Folsom AR| title=Relationship of folate, vitamin B-6, vitamin B-12, and methionine intake to incidence of colorectal cancers. | journal=Nutr Cancer | year= 2002 | volume= 43 | issue= 2 | pages= 152-8 | pmid=12588695 | doi=10.1207/S15327914NC432_5 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12588695 }} </ref>
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| | '''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<ref name="pmid12588695">{{cite journal| author=Harnack L, Jacobs DR, Nicodemus K, Lazovich D, Anderson K, Folsom AR| title=Relationship of folate, vitamin B-6, vitamin B-12, and methionine intake to incidence of colorectal cancers. | journal=Nutr Cancer | year= 2002 | volume= 43 | issue= 2 | pages= 152-8 | pmid=12588695 | doi=10.1207/S15327914NC432_5 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12588695 }} </ref>
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| | '''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<ref name="pmid19088354">{{cite journal| author=Botteri E, Iodice S, Bagnardi V, Raimondi S, Lowenfels AB, Maisonneuve P| title=Smoking and colorectal cancer: a meta-analysis. | journal=JAMA | year= 2008 | volume= 300 | issue= 23 | pages= 2765-78 | pmid=19088354 | doi=10.1001/jama.2008.839 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19088354 }} </ref>
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| | '''Uretercolic Anastomoses'''||There is increased risk of neoplasia in close proximity to the ureteric [[stoma]]<ref name="pmid7104616">{{cite journal| author=Stewart M, Macrae FA, Williams CB| title=Neoplasia and ureterosigmoidostomy: a colonoscopy survey. | journal=Br J Surg | year= 1982 | volume= 69 | issue= 7 | pages= 414-6 | pmid=7104616 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7104616 }} </ref>
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| | '''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{<ref name="pmid15644544">{{cite journal| author=Chao A, Thun MJ, Connell CJ, McCullough ML, Jacobs EJ, Flanders WD et al.| title=Meat consumption and risk of colorectal cancer. | journal=JAMA | year= 2005 | volume= 293 | issue= 2 | pages= 172-82 | pmid=15644544 | doi=10.1001/jama.293.2.172 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15644544 }} </ref><ref name="pmid10378216">{{cite journal| author=Glade MJ| title=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. | journal=Nutrition | year= 1999 | volume= 15 | issue= 6 | pages= 523-6 | pmid=10378216 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10378216 }} </ref>
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| | '''Coronary Heart Disease'''||The presence of [[coronary heart disease]] has been associated with an increased risk of CRC{<ref name="pmid17895457">{{cite journal| author=Chan AO, Jim MH, Lam KF, Morris JS, Siu DC, Tong T et al.| title=Prevalence of colorectal neoplasm among patients with newly diagnosed coronary artery disease. | journal=JAMA | year= 2007 | volume= 298 | issue= 12 | pages= 1412-9 | pmid=17895457 | doi=10.1001/jama.298.12.1412 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17895457 }} </ref>
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| | '''Sedentary Lifestyle'''||Regular exercise stimulates peristalsis, thereby decreasing transit time for [[carcinogenic]] substances in the colon<ref name="pmid24569462">{{cite journal| author=Lynch BM, Boyle T| title=Distinguishing sedentary from inactive: implications for meta-analyses. | journal=Br J Cancer | year= 2014 | volume= 111 | issue= 11 | pages= 2202-3 | pmid=24569462 | doi=10.1038/bjc.2014.106 | pmc=PMC4260011 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24569462 }} </ref>
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| | '''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<ref name="pmid11950810">{{cite journal| author=Evans HS, Møller H, Robinson D, Lewis CM, Bell CM, Hodgson SV| title=The risk of subsequent primary cancers after colorectal cancer in southeast England. | journal=Gut | year= 2002 | volume= 50 | issue= 5 | pages= 647-52 | pmid=11950810 | doi= | pmc=PMC1773208 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11950810 }} </ref>
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| ==References== | | ==References== |
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| [[Category:Disease]] | | [[Category:Disease]] |
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| [[Category:Types of cancer]] | | [[Category:Types of cancer]] |
| [[Category:Conditions diagnosed by stool test]] | | [[Category:Conditions diagnosed by stool test]] |
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