Colorectal cancer risk factors: Difference between revisions

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'''Editor(s)-in-Chief:''' [[C. Michael Gibson]], M.S.,M.D. [mailto:mgibson@perfuse.org]  Phone:617-632-7753; Elliot B. Tapper, M.D., Beth Israel Deaconess Medical Center
__NOTOC__
{{Colon cancer}}
{{Colon cancer}}
To view the risk factors of familial adenomatous polyposis (FAP), click [[Familial adenomatous polyposis risk factors|'''here''']]<br>
To view the risk factors of hereditary nonpolyposis colorectal cancer (HNPCC), click [[Hereditary nonpolyposis colorectal cancer risk factors|'''here''']]<br><br>
{{CMG}} {{AE}} Saarah T. Alkhairy, M.D.


==Overview==
==Overview==
There are both [[genetic]] and environmental factors that can increase the risk of colorectal carcinoma (CRC). Some of the [[Genetics|genetic]] risk factors are [[familial adenomatous polyposis]] and [[Hereditary nonpolyposis colorectal cancer|hereditary non-polyposis colorectal cancer]]. Some environmental risk factors are personal/family history, history of [[inflammatory bowel disease]], [[Diet (nutrition)|diet]], [[alcohol]], [[cigarette smoking]], [[race]], and gender.


==Risk factors==
==Colorectal Cancer Risk Factors==
The lifetime risk of developing colon cancer in the United States is about 7%. Certain factors increase a person's risk of developing the disease. These include:
The causes and the risk factors for colorectal carcinoma are the similar. There are both [[genetic]] and environmental factors that can increase the risk 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 (gene)|FAP]] and [[Hereditary nonpolyposis colorectal cancer|HNPCC]] are the most common risk factors 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>
* Age. The risk of developing colorectal cancer 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-americans, however, tends to occur earlier.<ref>Agrawal S et al. Colorectal cancer in African Americans. Am J Gastroenterol. 2005 Mar;100(3):515-23.</ref>
* [[Colorectal polyp|Polyps]] of the colon, particularly tubulovillous or villous adenomatous polyps, are a risk factor for colon cancer.  The removal of colon polyps at the time of colonoscopy reduces the subsequent risk of colon cancer.
* History of cancer. Individuals who have previously been diagnosed and treated for colon cancer are at risk for developing colon cancer in the future. Women who have had cancer of the ovary, uterus, or breast are at higher risk of developing colorectal cancer.
* Heredity:
** Family history of colon cancer, especially in a close relative before the age of 55 or multiple relatives
** [[Familial adenomatous polyposis]] (FAP) carries a near ''100%'' risk of developing colorectal cancer by the age of 40 if untreated
** [[Hereditary nonpolyposis colorectal cancer]] (HNPCC) or Lynch syndrome
* Long-standing [[ulcerative colitis]] or [[Crohn's disease]] of the colon, approximately 30% after 25 years if the entire colon is involved
* Smoking.  Smokers are more likely to die of colorectal cancer than non-smokers.  An [[American Cancer Society]] study found that "Women who smoked were more than 40% more likely to die from colorectal cancer than women who never had smoked. Male smokers had more than a 30% increase in risk of dying from the disease compared to men who never had smoked."<ref>[http://www.cancer.org/docroot/NWS/content/NWS_1_1x_Smoking_Linked_to_Increased_Colorectal_Cancer_Risk.asp American Cancer Society ''Smoking Linked to Increased Colorectal Cancer Risk - New Study Links Smoking to Increased Colorectal Cancer Risk'' [[2000-12-06]]]</ref>
* Diet. Studies show that a diet high in red meat<ref>Chao A, Thun MJ, Connell CJ, McCullough ML, Jacobs EJ, Flanders WD, Rodriguez C, Sinha R, Calle EE. ''Meat consumption and risk of colorectal cancer.'' JAMA 2005;293:172-82. PMID 15644544.</ref> and low in fresh fruit, vegetables, poultry and fish increases the risk of colorectal cancer. In June 2005, a study by the [[European Prospective Investigation into Cancer and Nutrition]] suggested that diets high in red and processed meat, as well as those low in fiber, are associated with an increased risk of colorectal cancer. Individuals who frequently ate fish showed a decreased risk.[http://news.bbc.co.uk/2/hi/health/4088824.stm] However, other studies have cast doubt on the claim that diets high in fiber decrease the risk of colorectal cancer; rather, low-fiber diet was associated with other risk factors, leading to confounding.<ref>[http://jama.ama-assn.org/cgi/content/abstract/294/22/2849 Park Y, Hunter DJ, Spiegelman D, Bergkvist L, Berrino F ''et al''. Dietary fiber intake and risk of colorectal cancer: a pooled analysis of prospective cohort studies. ''JAMA'' 2005;294:2849-57. PMID 16352792.]</ref> The nature of the relationship between dietary fiber and risk of colorectal cancer remains controversial.
* Virus. Exposure to some viruses (such as particular strains of [[human papilloma virus]]) may be associated with colorectal cancer.<ref>Pérez LO, Abba MC, Laguens RM, Golijow CD. Analysis of adenocarcinoma of the colon and rectum: detection of human papillomavirus (HPV) DNA by polymerase chain reaction. Colorectal Dis. 2005 Sep;7(5):492-5.</ref>
*Alcohol. See the subsection below.
* [[Primary sclerosing cholangitis]] offers a risk independent to [[ulcerative colitis]]
* Low [[selenium]].<ref>Salonen JT et al. ASSOCIATION BETWEEN SERUM SELENIUM AND THE RISK OF CANCER. Am. J. Epidemiol 1984;120(3):342-349</ref>
* Inflammatory Bowel Disease. <ref name=AMN>{{cite web | author = Gregory L. Brotzman and Russell G. Robertson | title =Colorectal Cancer Risk Factors | work =Colorectal Cancer | url=http://www.health.am/cr/colorectal-cancer/ | year = 2006 | publsiher=Armenian Health Network, Health.am | accessdate=2008-01-16}}</ref> <ref name=CA>{{cite journal | author = Jerome J. DeCosse, MD; George J. Tsioulias, MD; Judish S. Jacobson, MPH | title =Colorectal cancer: detection, treatment, and rehabilitation| work =Colorectal cancer: detection, treatment, and rehabilitation | url=http://caonline.amcancersoc.org/cgi/reprint/44/1/27.pdf | year = 1994 | month= Feb | publsiher=A Cancer Journal for Clinicians | accessdate=2008-01-16}}</ref> About one percent of colorectal cancer patients have a history of chronic ulcerative colitis. The risk of developing colorectal cancer varies inversely with the age of onset of the colitis and directly with the extent of colonic involvement and the duration of active disease. Patients with colorectal Crohn's disease have a more than average risk of colorectal cancer, but less than that of patients with ulcerative colitis. <ref>Hamilton SR. ''Colorectal Carcinoma in patients with Crohn's Disease.'' Gastroenterology 1985; 89; 398-407</ref>
* Environmental Factors. <ref name="AMN" /> Industrialized countries are at a relatively increased risk compared to less developed countries or countries that traditionally had high-fiber/low-fat diets. Studies of migrant populations have revealed a role for environmental factors, particularly dietary, in the etiology of colorectal cancers. Genetic factors and inflammatory bowel disease also place certain individuals at increased risk. <ref>Levin KE, Dozois RR. Department of Surgery, Mayo Clinic, Rochester, Minnesota 55905 ''Epidemiology of large bowel cancer.'' World J Surg. 1991 Sep-Oct;15(5):562-7. PMID 1949852.</ref>
* Exogenous Hormones. The differences in the time trends in colorectal cancer in males and females could be explained by cohort effects in exposure to some sex-specific risk factor; one possibility that has been suggested is exposure to estrogens <ref name=else>{{cite journal | author = DO SANTOS SILVA I. ; SWERDLOW A. J.  | title =Sex  differences  in  time  trends  of colorectal cancer in England and Wales: the possible effect of female hormonal factors. | work =Familial relative risk of colorectal cancer: a population-based study | url=http://cat.inist.fr/?aModele=afficheN&cpsidt=2995435| year = 2007 | publsiher=British journal of cancer |issue = ISSN 0007-0920 }}</ref>. There is, however, little evidence of an influence of endogenous hormones on the risk of colorectal cancer. In contrast,there is evidence that exogenous estrogens such as hormone replacement therapy (HRT), tamoxifen, or oral contraceptives might be associated with colorectal tumors. <ref>Beral V, Banks E, Reeves G, Appleby P. ''Use of HRT and the subsequent risk of cancer.'' Imperial Cancer Research Fund Cancer Epidemiology Unit, Oxford, UK. 1999;4(3):191-210; discussion 210-5. PMID 10695959.</ref> 


=== Alcohol ===
===Genetic Risk Factors===
On its colorectal cancer page, the [[National Cancer Institute]] does not list alcohol as a risk factor<ref>[http://www.cancer.gov/cancertopics/wyntk/colon-and-rectum/page4 Colorectal Cancer: Who's at Risk?] (National Institutes of Health: National Cancer Institute)</ref>: however, on another page it states, "Heavy alcohol use may also increase the risk of colorectal cancer" <ref>[[National Cancer Institute]] (NCI) Cancer Trends Progress Report [http://progressreport.cancer.gov/doc_detail.asp?pid=1&did=2005&chid=21&coid=206&mid= Alcohol Consumption]</ref>
The table below lists the [[genetic]] risk factors for colorectal carcinoma:<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><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>
{| style="border:#c9c9c9 1px solid; margin: 1em 1em 1em 0; border-collapse: collapse;" cellspacing="0" cellpadding="4" {{table}}
| style="background:#f0f0f0;" align="center" align="center" style="background:#4479BA; color: #FFFFFF;" + |'''Genetic Risk Factor'''


The NIAAA reports that: "Epidemiologic studies have found a small but consistent dose-dependent association between alcohol consumption and colorectal cancer<ref>Longnecker, M.P. Alcohol consumption in relation to risk of cancers of the breast and large bowel. ''Alcohol Health & Research World'' ''16(3)':223-229, 1992.</ref><ref>[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=2151680 Longnecker, M.P.; Orza, M.J.; Adams, M.E.; Vioque, J.; and Chalmers, T.C. A meta-analysis of alcoholic beverage consumption in relation to risk of colorectal cancer] ''Cancer Causes and Control'' ''1(1)'':59-68, 1990.</ref>even when controlling for fiber and other dietary factors.<ref>[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3808969&dopt=Abstract Kune, S.; Kune, G.A.; and Watson, L.F. Case-control study of alcoholic beverages as etiological factors: The Melbourne Colorectal Cancer Study] ''Nutrition and Cancer'' ''9(1)'':43-56, 1987.</ref><ref>[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3007842&dopt=Abstract Potter, J.D., and McMichael, A.J. Diet and cancer of the colon and rectum: A case-control study] ''Journal of the National Cancer Institute'' ''76(4)'':557-569, 1986.</ref>  Despite the large number of studies, however, causality cannot be determined from the available data."<ref name=aa21>[[National Institute on Alcohol Abuse and Alcoholism]] [http://pubs.niaaa.nih.gov/publications/aa21.htm Alcohol and Cancer - Alcohol Alert No. 21-1993]</ref>
| style="background:#f0f0f0;" align="center" align="center" style="background:#4479BA; color: #FFFFFF;" + |'''Description'''


"Heavy alcohol use may also increase the risk of colorectal cancer" (NCI). One study found that "People who drink more than 30 grams of alcohol per day (and especially those who drink more than 45 grams per day) appear to have a slightly higher risk for colorectal cancer."<ref>[http://www.annals.org/cgi/content/summary/140/8/603 Alcohol Consumption and the Risk for Colorectal Cancer] 20 April 2004</ref><ref>[http://www.annals.org/cgi/reprint/140/8/603.pdf Alcohol Intake and Colorectal Cancer: A Pooled Analysis of 8 Cohort Studies]</ref>  Another found that "The consumption of one or more alcoholic beverages a day at baseline was associated with approximately a 70% greater risk of colon cancer."<ref>Boston University [http://www.bu.edu/act/alcoholandhealth/issues/issue_may05/saitz_su.html "Alcohol May Increase the Risk of Colon Cancer"]</ref><ref>Su LJ, Arab L. [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15623458 Alcohol consumption and risk of colon cancer: evidence from the National Health and Nutrition Examination Survey I Epidemiologic Follow-Up Study]. ''Nutr and Cancer''.  2004;50(2):111–119.</ref><ref>Cho E, Smith-Warner SA, Ritz J, van den Brandt PA, Colditz GA, Folsom AR, Freudenheim JL, Giovannucci E, Goldbohm RA, Graham S, Holmberg L, Kim DH, Malila N, Miller AB, Pietinen P, Rohan TE, Sellers TA, Speizer FE, Willett WC, Wolk A, Hunter DJ  [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?itool=abstractplus&db=pubmed&cmd=Retrieve&dopt=abstractplus&list_uids=15096331 Alcohol intake and colorectal cancer: a pooled analysis of 8 cohort studies] ''Ann Intern Med'' 2004 Apr 20;140(8):603-13</ref>
|-


One study found that "While there was a more than twofold increased risk of significant colorectal neoplasia in people who drink spirits and beer, people who drank wine had a lower risk. In our sample, people who drank more than eight servings of beer or spirits per week had at least a one in five chance of having significant colorectal neoplasia detected by screening colonoscopy.".<ref>Joseph C. Anderson, Zvi Alpern, Gurvinder Sethi, Catherine R. Messina, Carole Martin, Patricia M. Hubbard, Roger Grimson,  Peter F. Ells, and Robert D. Shaw [http://www.amjgastro.com/showContent.asp?DID=4&SessionGUID=B9E28C55-3C9E-4DAC-9DBD-A5DECC905F45&id=ajg_4183292005&type=abstract Prevalence and Risk of Colorectal Neoplasia in Consumers of Alcohol in a Screening Population] ''Am J Gastroenterol'' Volume 100 Issue 9 Page 2049 Date September 2005</ref>  
| '''[[Familial Adenomatous Polyposis|Familial Adenomatous Polyposis (FAP)]]'''||
* Autosomal dominant inheritance
* Other variants include [[Gardner's syndrome]], [[Turcot syndrome|Turcot's syndrome]], and attenuated adenomatous polyposis coli
* Caused by germlines mutations in the [[APC gene]]
* Colonic cancer occurs in 90% of untreated individuals around 45 years
To view [[Gardner's syndrome]], [[Turcot syndrome|Turcot's syndrome]], and attenuated adenomatous polyposis coli , click [[Hereditary nonpolyposis colorectal cancer classification|'''here''']]<br>
|-


Other research suggests that "to minimize your risk of developing colorectal cancer, it's best to drink in moderation"<ref name=aa21/>
| '''MUTYH-associated Polyposis (MAP)'''||
* Autosomal resistant inheritance
* Caused by bi-allelic germline [[mutations]] in the [[Base excision repair|base excision repair gene]] mutY homolog (MYH or MUTYH)


Drinking may be a cause of earlier onset of colorectal cancer.<ref>Brown, Anthony J. [http://www.oncolink.com/resources/article.cfm?c=3&s=8&ss=23&id=12988&month=03&year=2006 Alcohol, tobacco, and male gender up risk of earlier onset colorectal cancer]</ref>
|-
 
| '''[[Hereditary nonpolyposis colorectal cancer|Lynch Syndrome]] AKA Hereditary Non-polyposis Colorectal Cancer (HNPCC)'''||
* Autosomal dominant inheritance
* Caused by a defect in one of the [[Mismatch repair|mismatch repair genes]], most commonly hMLH1, hMSH2, hMSH6, or PMS2
* Mean age at initial cancer diagnosis is around 48 years
 
|}
 
===Environmental Risk Factors===
The table below lists the environmental risk factors for colorectal carcinoma:<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. 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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><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><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><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><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><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><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><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><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><ref>{{Cite journal
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}}</ref><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><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><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><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><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><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><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>
{| style="border:#c9c9c9 1px solid; margin: 1em 1em 1em 0; border-collapse: collapse;" cellspacing="0" cellpadding="4" {{table}}
| style="background:#f0f0f0;" align="center" align="center" style="background:#4479BA; color: #FFFFFF;" + |'''Environmental Risk Factor'''
 
| style="background:#f0f0f0;" align="center" align="center" style="background:#4479BA; color: #FFFFFF;" + |'''Description'''
 
|-
 
| '''Family History'''||Risk increases with number of family members affected and the age of diagnosis
* If there is a single affected first-degree relative with CRC; the risk further increases if two first-degree relatives have CRC diagnosis
* If age of diagnosis is less than 50-60 years, the risk significantly increases especially if the family member has an [[Adenomatous Polyposis Coli|adenomatous colonic polyp]]
 
|-
 
| '''Personal History'''||Risk increases if there is a personal history of CRC or [[adenomatous polyps]], particularly:
* If they are multiple [[polyps]] >1 cm, or
* If the polyps are [[Villous adenoma|villous]] or [[Tubular adenoma|tubulovillous]]
 
|-
 
| '''[[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
 
|-
 
| '''[[Crohn's disease|Crohn's Disease]]'''||There is an increased risk:
* If 1/3rd or more of the [[Colon (anatomy)|colonic]] mucosa is involved
 
|-
 
| '''Age'''||The risk of developing CRC increases with age;
* Majority of 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
 
|-
 
| '''Abdominal Radiation'''||
* Adult survivors of childhood malignancy who received [[abdominal]] [[Radiation therapy|radiation]] are at significant risk
 
|-
 
| '''Race'''||The African American race has the highest CRC race of all the ethnic groups
* The mortality is 20% higher in the African American race compared to the Caucasian race
 
|-
 
| '''Gender'''||
* CRC mortality is about 20-40 percent higher in men than in women
 
|-
 
| '''Acromegaly'''||
* Patients with [[acromegaly]] are more likely to have multiple [[adenomatous polyps]]
 
|-
 
| '''Immunosuppression'''||
* [[Immunosuppression]] increases the risk of developing CRC, for example in [[renal transplantation]]
 
|-
 
| '''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 [[Colon (anatomy)|colonic]] mucosal cells and stimulates colonic [[tumor]] cells
 
|-
 
| '''Alcohol'''||
* The elevated risk may be related to interference of [[folate]] absorption by [[alcohol]] and decreased folate intake
 
|-
 
| '''Obesity'''||Every 5 kg/m2 increase in BMI was associated with:
* Twenty four percent increased incidence of both [[Colorectal cancer|colon]] and [[rectal cancer]] in men
* Nine percent higher incidence of colon cancer in women
 
|-
 
| '''Cigarette Smoking'''||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 [[Colorectal cancer|colon]]
 
|-
 
| '''Uretercolic Anastomoses'''||
* There is increased risk of [[neoplasia]] in close proximity to the ureteric [[stoma]]
 
|-
 
| '''Diet'''||Diets associated with an increased risk of CRC include:
* Long-term consumption of red meat or processed meats
* Diets low in vegetables and high in fats
 
|-
 
| '''Coronary Heart Disease'''||
* The presence of [[coronary heart disease]] has been associated with an increased risk of CRC
|-
 
| '''Sedentary Lifestyle'''||
* Regular exercise stimulates peristalsis, thereby decreasing transit time for [[carcinogenic]] substances in the colon
|-
 
| '''Other cancers'''||The following cancers have been associated with an CRC especially if the first diagnosis was made at an early age:
* [[Ovarian]]
* Endometrial
* Breast cancer
|}
 
==References==
{{Reflist|2}}
 
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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

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 similar. 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]

Genetic Risk Factors

The table below lists the genetic risk factors for colorectal carcinoma:[3][4]

Genetic Risk Factor Description
Familial Adenomatous Polyposis (FAP)
  • Autosomal dominant inheritance
  • Other variants include Gardner's syndrome, Turcot's syndrome, and attenuated adenomatous polyposis coli
  • Caused by germlines mutations in the APC gene
  • Colonic cancer occurs in 90% of untreated individuals around 45 years

To view Gardner's syndrome, Turcot's syndrome, and attenuated adenomatous polyposis coli , click here

MUTYH-associated Polyposis (MAP)
Lynch Syndrome AKA Hereditary Non-polyposis Colorectal Cancer (HNPCC)
  • Autosomal dominant inheritance
  • Caused by a defect in one of the mismatch repair genes, most commonly hMLH1, hMSH2, hMSH6, or PMS2
  • Mean age at initial cancer diagnosis is around 48 years

Environmental Risk Factors

The table below lists the environmental risk factors for colorectal carcinoma:[5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23]

Environmental Risk Factor Description
Family History Risk increases with number of family members affected and the age of diagnosis
  • If there is a single affected first-degree relative with CRC; the risk further increases if two first-degree relatives have CRC diagnosis
  • If age of diagnosis is less than 50-60 years, the risk significantly increases especially if the family member has an adenomatous colonic polyp
Personal History Risk increases if there is a personal history of CRC or adenomatous polyps, particularly:
Ulcerative Colitis The increase in risk begins about 8 to 10 years after the initial diagnosis of pancolitis and at 15 to 20 years
Crohn's Disease There is an increased risk:
  • If 1/3rd or more of the colonic mucosa is involved
Age The risk of developing CRC increases with age;
  • Majority of 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
Abdominal Radiation
  • Adult survivors of childhood malignancy who received abdominal radiation are at significant risk
Race The African American race has the highest CRC race of all the ethnic groups
  • The mortality is 20% higher in the African American race compared to the Caucasian race
Gender
  • CRC mortality is about 20-40 percent higher in men than in women
Acromegaly
Immunosuppression
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
Alcohol
  • The elevated risk may be related to interference of folate absorption by alcohol and decreased folate intake
Obesity Every 5 kg/m2 increase in BMI was associated with:
  • Twenty four percent increased incidence of both colon and rectal cancer in men
  • Nine percent higher incidence of colon cancer in women
Cigarette Smoking Risk of developing CRC was increased among cigarette smokers compared to those who never smoked;
Uretercolic Anastomoses
  • There is increased risk of neoplasia in close proximity to the ureteric stoma
Diet Diets associated with an increased risk of CRC include:
  • Long-term consumption of red meat or processed meats
  • Diets low in vegetables and high in fats
Coronary Heart Disease
Sedentary Lifestyle
  • Regular exercise stimulates peristalsis, thereby decreasing transit time for carcinogenic substances in the colon
Other cancers The following cancers have been associated with an CRC especially if the first diagnosis was made at an early age:

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. ↑ 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.
  6. ↑ 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.
  7. ↑ 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.
  8. ↑ 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.
  9. ↑ 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.
  10. ↑ 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.
  11. ↑ 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.
  12. ↑ 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.
  13. ↑ 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.
  14. ↑ Giovannucci E (1995). "Insulin and colon cancer". Cancer Causes Control. 6 (2): 164–79. PMID 7749056.
  15. ↑ 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.
  16. ↑ Carmen Jochem & Michael Leitzmann (2016). "Obesity and Colorectal Cancer". Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer. 208: 17–41. doi:10.1007/978-3-319-42542-9_2. PMID 27909900.
  17. ↑ 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.
  18. ↑ Stewart M, Macrae FA, Williams CB (1982). "Neoplasia and ureterosigmoidostomy: a colonoscopy survey". Br J Surg. 69 (7): 414–6. PMID 7104616.
  19. ↑ 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.
  20. ↑ 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.
  21. ↑ 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.
  22. ↑ 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.
  23. ↑ 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.


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