| H00020 | |
| H番号 | H00020 |
| 名称 | 結腸・直腸癌; 大腸癌 |
| 概要 | Colorectal cancer (CRC) is the second largest cause of cancer-related deaths in Western countries. CRC arises from the colorectal epithelium as a result of the accumulation of genetic alterations in defined oncogenes and tumour suppressor genes (TSG). Two major mechanisms of genomic instability have been identified in sporadic CRC progression. The first, known as chromosomal instability (CIN), results from a series of genetic changes that involve the activation of oncogenes such as K-ras and inactivation of TSG such as p53, DCC/Smad4, and APC. The second, known as microsatellite instability (MSI), results from inactivation of the DNA mismatch repair genes MLH1 and/or MSH2 by hypermethylation of their promoter, and secondary mutation of genes with coding microsatellites, such as transforming growth factor receptor II (TGF-RII) and BAX. Hereditary syndromes have germline mutations in specific genes (mutation in the tumour suppressor gene APC on chromosome 5q in FAP, mutated DNA mismatch repair genes in HNPCC). |
| カテゴリ | がん 疾患パスウェイ hsa05210 大腸癌 |
| ネットワーク | nt06260 Colorectal cancer nt06503 Mismatch repair nt06505(H00020) WNT signaling nt06507(H00020) TGFB signaling nt06515(H00020) Regulation of kinetochore-microtubule interactions nt06524(H00020) Apoptosis |
| 病因遺伝子 | (HNPCC) MLH1 [HSA:4292] [KO:K08734] (HNPCC) MLH3 [HSA:27030] [KO:K08739] (HNPCC) MSH2 [HSA:4436] [KO:K08735] (HNPCC) MSH6 [HSA:2956] [KO:K08737] (HNPCC) TGFBR2 [HSA:7048] [KO:K04388] (FAP) APC [HSA:324] [KO:K02085] (FAP) MSH3 [HSA:4437] [KO:K08736] (PPAP) POLD1 [HSA:5424] [KO:K02327] (PPAP) POLE [HSA:5426] [KO:K02324] DCC [HSA:1630] [KO:K06765] KRAS [HSA:3845] [KO:K07827] GALNT12 [HSA:79695] [KO:K00710] SMAD7 [HSA:4092] [KO:K19631] SMAD4 [HSA:4089] [KO:K04501] SMAD2 [HSA:4087] [KO:K04500] BAX [HSA:581] [KO:K02159] AXIN2 [HSA:8313] [KO:K04385] BRAF [HSA:673] [KO:K04365] CCND1 [HSA:595] [KO:K04503] CHEK2 [HSA:11200] [KO:K06641] CTNNB1 [HSA:1499] [KO:K02105] FLCN [HSA:201163] [KO:K09594] PIK3CA [HSA:5290] [KO:K00922] TP53 [HSA:7157] [KO:K04451] BUB1 [HSA:699] [KO:K02178] BUB1B [HSA:701] [KO:K06637] AURKA [HSA:6790] [KO:K11481] EGF (overexpression) [HSA:1950] [KO:K04357] TGFA (overexpression) [HSA:7039] [KO:K08774] EREG (overexpression) [HSA:2069] [KO:K09784] AREG (overexpression) [HSA:374] [KO:K09782] |
| 病原体 | - |
| 環境要因 | - |
| 発癌物質 | - |
| 治療薬 | マイトマイシンC [DR:D00208] ホリナートカルシウム [DR:D01211] レボホリナートカルシウム水和物 [DR:D11555] シクロホスファミド水和物 [DR:D00287] ニムスチン塩酸塩 [DR:D01059] フルオロウラシル [DR:D00584] カペシタビン [DR:D01223] ドキシフルリジン [DR:D01309] シタラビン [DR:D00168] テガフール・ウラシル [DR:D02131] テガフール・ギメラシル・オテラシルカリウム [DR:D06399] ドキソルビシン塩酸塩 [DR:D01275] イリノテカン塩酸塩水和物 [DR:D01061] エンコラフェニブ [DR:D11053] (BRAF遺伝子変異陽性) ビニメチニブ [DR:D10604] (BRAF遺伝子変異陽性) レゴラフェニブ水和物 [DR:D10137] トラスツズマブ [DR:D03257] (HER2陽性) ペルツズマブ [DR:D05446] (HER2陽性) セツキシマブ [DR:D03455] (RAS遺伝子野生型) パニツムマブ [DR:D05350] (KRAS野生型) ニボルマブ [DR:D10316] (MSI-High) ペムブロリズマブ [DR:D10574] (MSI-High) ベバシズマブ [DR:D06409] ラムシルマブ [DR:D09371] イピリムマブ [DR:D04603] (MSI-High) オキサリプラチン [DR:D01790] アフリベルセプトベータ [DR:D10819] トリフルリジン・チピラシル塩酸塩 [DR:D10526] |
| コメント | - |
| リンク | ICD-11: 2B90 2B91 2B92 ICD-10: C18 C19 C20 MeSH: D015179 OMIM: 114500 608812 612229 |
| 文献 | PMID:11477132 著者 Houlston RS. タイトル What we could do now: molecular pathology of colorectal cancer. 雑誌 Mol Pathol 54:206-14 (2001) DOI:10.1136/mp.54.4.206 PMID:12621137 著者 Lynch HT, de la Chapelle A. タイトル Hereditary colorectal cancer. 雑誌 N Engl J Med 348:919-32 (2003) DOI:10.1056/NEJMra012242 PMID:15000146 (TP53, APC, MSH3, MSH6, CTNNB1, KRAS, TGFBR2, BAX) 著者 Grady WM. タイトル Genomic instability and colon cancer. 雑誌 Cancer Metastasis Rev 23:11-27 (2004) DOI:10.1023/A:1025861527711 PMID:16555243 (DCC, SMAD2/4, TP53, APC, MLH1, MSH2, MSH6, CTNNB1, KRAS, TGFBR2, BAX) 著者 Soreide K, Janssen EA, Soiland H, Korner H, Baak JP. タイトル Microsatellite instability in colorectal cancer. 雑誌 Br J Surg 93:395-406 (2006) DOI:10.1002/bjs.5328 PMID:15310786 (DCC) 著者 Mehlen P, Fearon ER. タイトル Role of the dependence receptor DCC in colorectal cancer pathogenesis. 雑誌 J Clin Oncol 22:3420-8 (2004) DOI:10.1200/JCO.2004.02.019 PMID:19617566 (GALNT12) 著者 Guda K, Moinova H, He J, Jamison O, Ravi L, Natale L, Lutterbaugh J, Lawrence E, Lewis S, Willson JK, Lowe JB, Wiesner GL, Parmigiani G, Barnholtz-Sloan J, Dawson DW, Velculescu VE, Kinzler KW, Papadopoulos N, Vogelstein B, Willis J, Gerken TA, Markowitz SD タイトル Inactivating germ-line and somatic mutations in polypeptide N-acetylgalactosaminyltransferase 12 in human colon cancers. 雑誌 Proc Natl Acad Sci U S A 106:12921-5 (2009) DOI:10.1073/pnas.0901454106 PMID:17934461 (SNAD7) 著者 Broderick P, Carvajal-Carmona L, Pittman AM, Webb E, Howarth K, Rowan A, Lubbe S, Spain S, Sullivan K, Fielding S, Jaeger E, Vijayakrishnan J, Kemp Z, Gorman M, Chandler I, Papaemmanuil E, Penegar S, Wood W, Sellick G, Qureshi M, Teixeira A, Domingo E, Barclay E, Martin L, Sieber O, Kerr D, Gray R, Peto J, Cazier JB, Tomlinson I, Houlston RS タイトル A genome-wide association study shows that common alleles of SMAD7 influence colorectal cancer risk. 雑誌 Nat Genet 39:1315-7 (2007) DOI:10.1038/ng.2007.18 PMID:26133394 (POLE, POLD1) 著者 Bellido F, Pineda M, Aiza G, Valdes-Mas R, Navarro M, Puente DA, Pons T, Gonzalez S, Iglesias S, Darder E, Pinol V, Soto JL, Valencia A, Blanco I, Urioste M, Brunet J, Lazaro C, Capella G, Puente XS, Valle L タイトル POLE and POLD1 mutations in 529 kindred with familial colorectal cancer and/or polyposis: review of reported cases and recommendations for genetic testing and surveillance. 雑誌 Genet Med 18:325-32 (2016) DOI:10.1038/gim.2015.75 PMID:7912978 著者 Hayashi Y, Widjono YW, Ohta K, Hanioka K, Obayashi C, Itoh K, Imai Y, Itoh H タイトル Expression of EGF, EGF-receptor, p53, v-erb B and ras p21 in colorectal neoplasms by immunostaining paraffin-embedded tissues. 雑誌 Pathol Int 44:124-30 (1994) DOI:10.1111/j.1440-1827.1994.tb01696.x PMID:11017067 (AXIN2) 著者 Liu W, Dong X, Mai M, Seelan RS, Taniguchi K, Krishnadath KK, Halling KC, Cunningham JM, Boardman LA, Qian C, Christensen E, Schmidt SS, Roche PC, Smith DI, Thibodeau SN タイトル Mutations in AXIN2 cause colorectal cancer with defective mismatch repair by activating beta-catenin/TCF signalling. 雑誌 Nat Genet 26:146-7 (2000) DOI:10.1038/79859 PMID:12198537 (BRAF, KRAS) 著者 Rajagopalan H, Bardelli A, Lengauer C, Kinzler KW, Vogelstein B, Velculescu VE タイトル Tumorigenesis: RAF/RAS oncogenes and mismatch-repair status. 雑誌 Nature 418:934 (2002) DOI:10.1038/418934a PMID:10667569 (CCND1) 著者 Kong S, Amos CI, Luthra R, Lynch PM, Levin B, Frazier ML タイトル Effects of cyclin D1 polymorphism on age of onset of hereditary nonpolyposis colorectal cancer. 雑誌 Cancer Res 60:249-52 (2000) PMID:12690581 (CHEK2) 著者 Meijers-Heijboer H, Wijnen J, Vasen H, Wasielewski M, Wagner A, Hollestelle A, Elstrodt F, van den Bos R, de Snoo A, Fat GT, Brekelmans C, Jagmohan S, Franken P, Verkuijlen P, van den Ouweland A, Chapman P, Tops C, Moslein G, Burn J, Lynch H, Klijn J, Fodde R, Schutte M タイトル The CHEK2 1100delC mutation identifies families with a hereditary breast and colorectal cancer phenotype. 雑誌 Am J Hum Genet 72:1308-14 (2003) DOI:10.1086/375121 PMID:12843323 (FLCN) 著者 Kahnoski K, Khoo SK, Nassif NT, Chen J, Lobo GP, Segelov E, Teh BT タイトル Alterations of the Birt-Hogg-Dube gene (BHD) in sporadic colorectal tumours. 雑誌 J Med Genet 40:511-5 (2003) DOI:10.1136/jmg.40.7.511 PMID:11317354 (MLH3) 著者 Lipkin SM, Wang V, Stoler DL, Anderson GR, Kirsch I, Hadley D, Lynch HT, Collins FS タイトル Germline and somatic mutation analyses in the DNA mismatch repair gene MLH3: Evidence for somatic mutation in colorectal cancers. 雑誌 Hum Mutat 17:389-96 (2001) DOI:10.1002/humu.1114 PMID:15016963 (PIK3CA) 著者 Samuels Y, Wang Z, Bardelli A, Silliman N, Ptak J, Szabo S, Yan H, Gazdar A, Powell SM, Riggins GJ, Willson JK, Markowitz S, Kinzler KW, Vogelstein B, Velculescu VE タイトル High frequency of mutations of the PIK3CA gene in human cancers. 雑誌 Science 304:554 (2004) DOI:10.1126/science.1096502 PMID:21139621 (EGF, TGFA, EREG, AREG) 著者 Di Fiore F, Sesboue R, Michel P, Sabourin JC, Frebourg T タイトル Molecular determinants of anti-EGFR sensitivity and resistance in metastatic colorectal cancer. 雑誌 Br J Cancer 103:1765-72 (2010) DOI:10.1038/sj.bjc.6606008 PMID:9521327 (BUB1, BUB1B) 著者 Cahill DP, Lengauer C, Yu J, Riggins GJ, Willson JK, Markowitz SD, Kinzler KW, Vogelstein B タイトル Mutations of mitotic checkpoint genes in human cancers. 雑誌 Nature 392:300-3 (1998) DOI:10.1038/32688 PMID:12881723 (AURKA) 著者 Ewart-Toland A, Briassouli P, de Koning JP, Mao JH, Yuan J, Chan F, MacCarthy-Morrogh L, Ponder BA, Nagase H, Burn J, Ball S, Almeida M, Linardopoulos S, Balmain A タイトル Identification of Stk6/STK15 as a candidate low-penetrance tumor-susceptibility gene in mouse and human. 雑誌 Nat Genet 34:403-12 (2003) DOI:10.1038/ng1220 |