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Familial colorectal cancer(CRC)

MedGen UID:
430218
Concept ID:
CN029768
Disease or Syndrome
Synonyms: COLON CANCER; COLORECTAL CANCER; CRC
 
Related genes: GALNT12, MLH3, AXIN2, TGFBR2, STK11, POLD1, PMS2, PMS1, MUTYH, MSH2, MLH1, SMAD7, SMAD4, EPCAM, MSH6, BMPR1A, APC

Definition

Colorectal cancer is a heterogeneous disease that is common in both men and women. In addition to lifestyle and environmental risk factors, gene defects can contribute to an inherited predisposition to CRC. CRC is caused by changes in different molecular pathogenic pathways, such as chromosomal instability, CpG island methylator phenotype, and microsatellite instability. Chromosome instability is the most common alteration and is present in almost 85% of all cases (review by Schweiger et al., 2013). Genetic Heterogeneity of Colorectal Cancer Mutations in a single gene result in a marked predisposition to colorectal cancer in 2 distinct syndromes: familial adenomatous polyposis (FAP; 175100) and hereditary nonpolyposis colorectal cancer (HNPCC; see 120435). FAP is caused by mutations in the APC gene (611731), whereas HNPCC is caused by mutations in several genes, including MSH2 (609309), MLH1 (120436), PMS1 (600258), PMS2 (600259), MSH6 (600678), TGFBR2 (190182), and MLH3 (604395). Epigenetic silencing of MSH2 results in a form of HNPCC (see HNPCC8, 613244). Other colorectal cancer syndromes include autosomal recessive adenomatous polyposis (608456), which is caused by mutations in the MUTYH gene (604933), and oligodontia-colorectal cancer syndrome (608615), which is caused by mutations in the AXIN2 gene (604025). The CHEK2 gene (604373) has been implicated in susceptibility to colorectal cancer in Finnish patients. A germline mutation in the PLA2G2A gene (172411) was identified in a patient with colorectal cancer. Germline susceptibility loci for colorectal cancer have also been identified. CRCS1 (608812) is conferred by mutation in the GALNT12 gene (610290) on chromosome 9q22; CRCS2 (611469) maps to chromosome 8q24; CRCS3 (612229) is conferred by variation in the SMAD7 gene (602932) on chromosome 18; CRCS4 (601228) is conferred by variation on 15q that causes increased and ectopic expression of the GREM1 gene (603054); CRCS5 (612230) maps to chromosome 10p14; CRCS6 (612231) maps to chromosome 8q23; CRCS7 (612232) maps to chromosome 11q23; CRCS8 (612589) maps to chromosome 14q22; CRCS9 (612590) maps to 16q22; CRCS10 (612591) is conferred by mutation in the POLD1 gene (174761) on chromosome 19q13; CRCS11 (612592) maps to chromosome 20p12; and CRCS12 (615083) is conferred by mutation in the POLE gene (174762) on chromosome 12q24. Somatic mutations in many different genes, including KRAS (190070), PIK3CA (171834), BRAF (164757), CTNNB1 (116806), FGFR3 (134934), AXIN2 (604025), AKT1 (164730), MCC (159350), MYH11 (160745), PARK2 (602544), and RNF43 (612482), have been identified in colorectal cancer. [from GTR]

Additional description

From OMIM
Colorectal cancer is a heterogeneous disease that is common in both men and women. In addition to lifestyle and environmental risk factors, gene defects can contribute to an inherited predisposition to CRC. CRC is caused by changes in different molecular pathogenic pathways, such as chromosomal instability, CpG island methylator phenotype, and microsatellite instability. Chromosome instability is the most common alteration and is present in almost 85% of all cases (review by Schweiger et al., 2013). Genetic Heterogeneity of Colorectal Cancer Mutations in a single gene result in a marked predisposition to colorectal cancer in 2 distinct syndromes: familial adenomatous polyposis (FAP; 175100) and hereditary nonpolyposis colorectal cancer (HNPCC; see 120435). FAP is caused by mutations in the APC gene (611731), whereas HNPCC is caused by mutations in several genes, including MSH2 (609309), MLH1 (120436), PMS1 (600258), PMS2 (600259), MSH6 (600678), TGFBR2 (190182), and MLH3 (604395). Epigenetic silencing of MSH2 results in a form of HNPCC (see HNPCC8, 613244). Other colorectal cancer syndromes include autosomal recessive adenomatous polyposis (608456), which is caused by mutations in the MUTYH gene (604933), and oligodontia-colorectal cancer syndrome (608615), which is caused by mutations in the AXIN2 gene (604025). The CHEK2 gene (604373) has been implicated in susceptibility to colorectal cancer in Finnish patients. A germline mutation in the PLA2G2A gene (172411) was identified in a patient with colorectal cancer. Germline susceptibility loci for colorectal cancer have also been identified. CRCS1 (608812) is conferred by mutation in the GALNT12 gene (610290) on chromosome 9q22; CRCS2 (611469) maps to chromosome 8q24; CRCS3 (612229) is conferred by variation in the SMAD7 gene (602932) on chromosome 18; CRCS4 (601228) is conferred by variation on 15q that causes increased and ectopic expression of the GREM1 gene (603054); CRCS5 (612230) maps to chromosome 10p14; CRCS6 (612231) maps to chromosome 8q23; CRCS7 (612232) maps to chromosome 11q23; CRCS8 (612589) maps to chromosome 14q22; CRCS9 (612590) maps to 16q22; CRCS10 (612591) is conferred by mutation in the POLD1 gene (174761) on chromosome 19q13; CRCS11 (612592) maps to chromosome 20p12; and CRCS12 (615083) is conferred by mutation in the POLE gene (174762) on chromosome 12q24. Somatic mutations in many different genes, including KRAS (190070), PIK3CA (171834), BRAF (164757), CTNNB1 (116806), FGFR3 (134934), AXIN2 (604025), AKT1 (164730), MCC (159350), MYH11 (160745), PARK2 (602544), and RNF43 (612482), have been identified in colorectal cancer.  http://www.omim.org/entry/114500

Term Hierarchy

Professional guidelines

PubMed

Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group.
Genet Med 2009 Jan;11(1):35-41. doi: 10.1097/GIM.0b013e31818fa2ff. PMID: 19125126Free PMC Article

Suggested Reading

Recent clinical studies

Etiology

Parfrey PS, Dicks E, Parfrey O, McNicholas PJ, Noseworthy H, Woods MO, Negriin C, Green J
Clin Genet 2017 May;91(5):672-682. Epub 2017 Mar 8 doi: 10.1111/cge.12877. PMID: 27696385Free PMC Article
Medina-Arana V, Rahy-Martín A, Delgado-Plasencia L, Martínez-Riera A, León-Ayllón D, Rodríguez-Castellano D, Bravo-Gutiérrez A, Fernández-Peralta A, González-Aguilera JJ
Colorectal Dis 2016 Nov;18(11):O388-O396. doi: 10.1111/codi.13532. PMID: 27671100
van Erp SJ, Leicher LW, Hennink SD, Ghorbanoghli Z, Breg SA, Morreau H, Nielsen M, Hardwick JC, Roukema JA, Langers AM, Cappel WHVTN, Vasen HF
Scand J Gastroenterol 2016 Oct;51(10):1227-32. Epub 2016 Jun 16 doi: 10.1080/00365521.2016.1193219. PMID: 27310819Free PMC Article
Yamaguchi T, Furukawa Y, Nakamura Y, Matsubara N, Ishikawa H, Arai M, Tomita N, Tamura K, Sugano K, Ishioka C, Yoshida T, Moriya Y, Ishida H, Watanabe T, Sugihara K; HNPCC Registry and Genetic Testing Project of the Japanese Society for Cancer of the Colon and Rectum.
Jpn J Clin Oncol 2015 Feb;45(2):153-9. Epub 2014 Nov 17 doi: 10.1093/jjco/hyu190. PMID: 25404568
Ku CS, Cooper DN, Wu M, Roukos DH, Pawitan Y, Soong R, Iacopetta B
Mod Pathol 2012 Aug;25(8):1055-68. Epub 2012 Apr 20 doi: 10.1038/modpathol.2012.62. PMID: 22522846

Diagnosis

Medina-Arana V, Rahy-Martín A, Delgado-Plasencia L, Martínez-Riera A, León-Ayllón D, Rodríguez-Castellano D, Bravo-Gutiérrez A, Fernández-Peralta A, González-Aguilera JJ
Colorectal Dis 2016 Nov;18(11):O388-O396. doi: 10.1111/codi.13532. PMID: 27671100
van Erp SJ, Leicher LW, Hennink SD, Ghorbanoghli Z, Breg SA, Morreau H, Nielsen M, Hardwick JC, Roukema JA, Langers AM, Cappel WHVTN, Vasen HF
Scand J Gastroenterol 2016 Oct;51(10):1227-32. Epub 2016 Jun 16 doi: 10.1080/00365521.2016.1193219. PMID: 27310819Free PMC Article
Yamaguchi T, Furukawa Y, Nakamura Y, Matsubara N, Ishikawa H, Arai M, Tomita N, Tamura K, Sugano K, Ishioka C, Yoshida T, Moriya Y, Ishida H, Watanabe T, Sugihara K; HNPCC Registry and Genetic Testing Project of the Japanese Society for Cancer of the Colon and Rectum.
Jpn J Clin Oncol 2015 Feb;45(2):153-9. Epub 2014 Nov 17 doi: 10.1093/jjco/hyu190. PMID: 25404568
Garre P, Martín L, Sanz J, Romero A, Tosar A, Bando I, Llovet P, Diaque P, García-Paredes B, Díaz-Rubio E, de la Hoya M, Caldés T
Clin Genet 2015 Jun;87(6):582-7. Epub 2014 Jun 18 doi: 10.1111/cge.12427. PMID: 24814045
Peng J, Xiao-ming M, Jian-qiu S, Zi-tao W, Lei F, He-juan A, Ying H, Shi-rong L
Chin Med Sci J 2010 Dec;25(4):228-32. PMID: 21232183

Therapy

Hennink SD, van der Meulen-de Jong AE, Wolterbeek R, Crobach AS, Becx MC, Crobach WF, van Haastert M, Ten Hove WR, Kleibeuker JH, Meijssen MA, Nagengast FM, Rijk MC, Salemans JM, Stronkhorst A, Tuynman HA, Vecht J, Verhulst ML, de Vos Tot Nederveen Cappel WH, Walinga H, Weinhardt OK, Westerveld D, Witte AM, Wolters HJ, Cats A, Veenendaal RA, Morreau H, Vasen HF
J Clin Oncol 2015 Dec 10;33(35):4188-93. Epub 2015 Nov 2 doi: 10.1200/JCO.2015.62.2035. PMID: 26527788
Quintero E, Carrillo M, Gimeno-García AZ, Hernández-Guerra M, Nicolás-Pérez D, Alonso-Abreu I, Díez-Fuentes ML, Abraira V
Gastroenterology 2014 Nov;147(5):1021-30.e1; quiz e16-7. Epub 2014 Aug 13 doi: 10.1053/j.gastro.2014.08.004. PMID: 25127679
van der Meulen-de Jong AE, Morreau H, Becx MC, Crobach LF, van Haastert M, ten Hove WR, Kleibeuker JH, Meijssen MA, Nagengast FM, Rijk MC, Salemans JM, Stronkhorst A, Tuynman HA, Vecht J, Verhulst ML, de Vos tot Nederveen Cappel WH, Walinga H, Weinhardt OK, Westerveld BD, Witte AM, Wolters HJ, Vasen HF
Gut 2011 Jan;60(1):73-6. Epub 2010 Sep 9 doi: 10.1136/gut.2010.217091. PMID: 20833659
Balmaña J, Castells A, Cervantes A; ESMO Guidelines Working Group.
Ann Oncol 2010 May;21 Suppl 5:v78-81. doi: 10.1093/annonc/mdq169. PMID: 20555108
Cotterchio M, Manno M, Klar N, McLaughlin J, Gallinger S
Cancer Causes Control 2005 Sep;16(7):865-75. doi: 10.1007/s10552-005-2370-3. PMID: 16132797

Prognosis

Parfrey PS, Dicks E, Parfrey O, McNicholas PJ, Noseworthy H, Woods MO, Negriin C, Green J
Clin Genet 2017 May;91(5):672-682. Epub 2017 Mar 8 doi: 10.1111/cge.12877. PMID: 27696385Free PMC Article
Sjöström O, Lindholm L, Tavelin B, Melin B
Fam Cancer 2016 Oct;15(4):543-51. doi: 10.1007/s10689-016-9867-7. PMID: 26935832Free PMC Article
Yamaguchi T, Furukawa Y, Nakamura Y, Matsubara N, Ishikawa H, Arai M, Tomita N, Tamura K, Sugano K, Ishioka C, Yoshida T, Moriya Y, Ishida H, Watanabe T, Sugihara K; HNPCC Registry and Genetic Testing Project of the Japanese Society for Cancer of the Colon and Rectum.
Jpn J Clin Oncol 2015 Feb;45(2):153-9. Epub 2014 Nov 17 doi: 10.1093/jjco/hyu190. PMID: 25404568
Quintero E, Carrillo M, Gimeno-García AZ, Hernández-Guerra M, Nicolás-Pérez D, Alonso-Abreu I, Díez-Fuentes ML, Abraira V
Gastroenterology 2014 Nov;147(5):1021-30.e1; quiz e16-7. Epub 2014 Aug 13 doi: 10.1053/j.gastro.2014.08.004. PMID: 25127679
Mesher D, Dove-Edwin I, Sasieni P, Vasen H, Bernstein I, Royer-Pokora B, Holinski-Feder E, Lalloo F, Evans DG, Forsberg A, Lindblom A, Thomas H
Int J Cancer 2014 Feb 15;134(4):939-47. Epub 2013 Aug 29 doi: 10.1002/ijc.28397. PMID: 23901040

Clinical prediction guides

Parfrey PS, Dicks E, Parfrey O, McNicholas PJ, Noseworthy H, Woods MO, Negriin C, Green J
Clin Genet 2017 May;91(5):672-682. Epub 2017 Mar 8 doi: 10.1111/cge.12877. PMID: 27696385Free PMC Article
van Erp SJ, Leicher LW, Hennink SD, Ghorbanoghli Z, Breg SA, Morreau H, Nielsen M, Hardwick JC, Roukema JA, Langers AM, Cappel WHVTN, Vasen HF
Scand J Gastroenterol 2016 Oct;51(10):1227-32. Epub 2016 Jun 16 doi: 10.1080/00365521.2016.1193219. PMID: 27310819Free PMC Article
Sjöström O, Lindholm L, Tavelin B, Melin B
Fam Cancer 2016 Oct;15(4):543-51. doi: 10.1007/s10689-016-9867-7. PMID: 26935832Free PMC Article
Shiovitz S, Copeland WK, Passarelli MN, Burnett-Hartman AN, Grady WM, Potter JD, Gallinger S, Buchanan DD, Rosty C, Win AK, Jenkins M, Thibodeau SN, Haile R, Baron JA, Marchand LL, Newcomb PA, Lindor NM; Colon Cancer Family Registry.
Br J Cancer 2014 Jul 29;111(3):598-602. Epub 2014 Jun 10 doi: 10.1038/bjc.2014.309. PMID: 24918813Free PMC Article
Peng J, Xiao-ming M, Jian-qiu S, Zi-tao W, Lei F, He-juan A, Ying H, Shi-rong L
Chin Med Sci J 2010 Dec;25(4):228-32. PMID: 21232183

Recent systematic reviews

Bellido F, Pineda M, Aiza G, Valdés-Mas R, Navarro M, Puente DA, Pons T, González S, Iglesias S, Darder E, Piñol V, Soto JL, Valencia A, Blanco I, Urioste M, Brunet J, Lázaro C, Capellá G, Puente XS, Valle L
Genet Med 2016 Apr;18(4):325-32. Epub 2015 Jul 2 doi: 10.1038/gim.2015.75. PMID: 26133394Free PMC Article
Balmaña J, Castells A, Cervantes A; ESMO Guidelines Working Group.
Ann Oncol 2010 May;21 Suppl 5:v78-81. doi: 10.1093/annonc/mdq169. PMID: 20555108
Kievit W, de Bruin JH, Adang EM, Ligtenberg MJ, Nagengast FM, van Krieken JH, Hoogerbrugge N
Clin Genet 2004 Apr;65(4):308-16. doi: 10.1111/j.1399-0004.2004.00220.x. PMID: 15025724
Johns LE, Houlston RS
Am J Gastroenterol 2001 Oct;96(10):2992-3003. doi: 10.1111/j.1572-0241.2001.04677.x. PMID: 11693338
Heriot AG, Murday V, Kumar D
J R Coll Surg Edinb 1999 Feb;44(1):13-5. PMID: 10079661

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