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DOI: 10.1055/s-0032-1313783
Oncologic Management of Hereditary Colorectal Cancer
Publication History
Publication Date:
30 May 2012 (online)
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Abstract
Colorectal cancer (CRC) is the second most common cancer in females and the third most common cancer diagnosed in males. Familial CRC comprises ~20 to 30% of all CRC cases. Lynch syndrome (LS), previously called hereditary nonpolyposis CRC (HNPCC), is the most common of the hereditary CRC syndromes. In this review, the oncological management of hereditary colorectal cancer from the medical oncologist perspective is discussed with special emphasis on Lynch syndrome. Lynch syndrome is characterized by the presence of germline mutations in the mismatch repair genes (MMR)-MSH2, MLH1, MSH6, and PMS2. The available data regarding the prognostic role of mismatch repair genes (MMR), the predictive role of MMR genes, and the implications of that in the management of patients with deficient MMR genes (dMMR/MSI-H) tumors including Lynch syndrome patients are also discussed.
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References
- 1 Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin 2011; 61 (2) 69-90
- 2 Power DG, Gloglowski E, Lipkin SM. Clinical genetics of hereditary colorectal cancer. Hematol Oncol Clin North Am 2010; 24 (5) 837-859
- 3 Hewish M, Lord CJ, Martin SA, Cunningham D, Ashworth A. Mismatch repair deficient colorectal cancer in the era of personalized treatment. Nat Rev Clin Oncol 2010; 7 (4) 197-208
- 4 Ogino S, Nosho K, Kirkner GJ , et al. CpG island methylator phenotype, microsatellite instability, BRAF mutation and clinical outcome in colon cancer. Gut 2009; 58 (1) 90-96
- 5 Popat S, Hubner R, Houlston RS. Systematic review of microsatellite instability and colorectal cancer prognosis. J Clin Oncol 2005; 23 (3) 609-618
- 6 Ribic CM, Sargent DJ, Moore MJ , et al. Tumor microsatellite-instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for colon cancer. N Engl J Med 2003; 349 (3) 247-257
- 7 Kim GP, Colangelo LH, Wieand HS , et al; National Cancer Institute. Prognostic and predictive roles of high-degree microsatellite instability in colon cancer: a National Cancer Institute-National Surgical Adjuvant Breast and Bowel Project Collaborative Study. J Clin Oncol 2007; 25 (7) 767-772
- 8 Sargent DJ, Marsoni S, Monges G , et al. Defective mismatch repair as a predictive marker for lack of efficacy of fluorouracil-based adjuvant therapy in colon cancer. J Clin Oncol 2010; 28 (20) 3219-3226
- 9 Carethers JM, Chauhan DP, Fink D , et al. Mismatch repair proficiency and in vitro response to 5-fluorouracil. Gastroenterology 1999; 117 (1) 123-131
- 10 Arnold CN, Goel A, Boland CR. Role of hMLH1 promoter hypermethylation in drug resistance to 5-fluorouracil in colorectal cancer cell lines. Int J Cancer 2003; 106 (1) 66-73
- 11 Fink D, Aebi S, Howell SB. The role of DNA mismatch repair in drug resistance. Clin Cancer Res 1998; 4 (1) 1-6
- 12 Meyers M, Wagner MW, Hwang HS, Kinsella TJ, Boothman DA. Role of the hMLH1 DNA mismatch repair protein in fluoropyrimidine-mediated cell death and cell cycle responses. Cancer Res 2001; 61 (13) 5193-5201
- 13 de Vos tot Nederveen Cappel WH, Meulenbeld HJ, Kleibeuker JH , et al. Survival after adjuvant 5-FU treatment for stage III colon cancer in hereditary nonpolyposis colorectal cancer. Int J Cancer 2004; 109 (3) 468-471
- 14 Efficacy of adjuvant fluorouracil and folinic acid in colon cancer. International Multicentre Pooled Analysis of Colon Cancer Trials (IMPACT) investigators. Lancet 1995; 345 (8955) 939-944
- 15 Hutchins G, Southward K, Handley K , et al. Value of mismatch repair, KRAS, and BRAF mutations in predicting recurrence and benefits from chemotherapy in colorectal cancer. J Clin Oncol 2011; 29 (10) 1261-1270
- 16 Elsaleh H, Iacopetta B. Microsatellite instability is a predictive marker for survival benefit from adjuvant chemotherapy in a population-based series of stage III colorectal carcinoma. Clin Colorectal Cancer 2001; 1 (2) 104-109
- 17 Hemminki A, Mecklin JP, Järvinen H, Aaltonen LA, Joensuu H. Microsatellite instability is a favorable prognostic indicator in patients with colorectal cancer receiving chemotherapy. Gastroenterology 2000; 119 (4) 921-928
- 18 Brueckl WM, Moesch C, Brabletz T , et al. Relationship between microsatellite instability, response and survival in palliative patients with colorectal cancer undergoing first-line chemotherapy. Anticancer Res 2003; 23 (2C) 1773-1777
- 19 Liang JT, Huang KC, Lai HS , et al. High-frequency microsatellite instability predicts better chemosensitivity to high-dose 5-fluorouracil plus leucovorin chemotherapy for stage IV sporadic colorectal cancer after palliative bowel resection. Int J Cancer 2002; 101 (6) 519-525
- 20 des Guetz G, Mariani P, Cucherousset J , et al. Microsatellite instability and sensitivitiy to FOLFOX treatment in metastatic colorectal cancer. Anticancer Res 2007; 27 (4C) 2715-2719
- 21 Vaisman A, Varchenko M, Umar A , et al. The role of hMLH1, hMSH3, and hMSH6 defects in cisplatin and oxaliplatin resistance: correlation with replicative bypass of platinum-DNA adducts. Cancer Res 1998; 58 (16) 3579-3585
- 22 Müller CI, Schulmann K, Reinacher-Schick A , et al; AIO Colorectal Study Group. Predictive and prognostic value of microsatellite instability in patients with advanced colorectal cancer treated with a fluoropyrimidine and oxaliplatin containing first-line chemotherapy. A report of the AIO Colorectal Study Group. Int J Colorectal Dis 2008; 23 (11) 1033-1039
- 23 Porschen R, Arkenau HT, Kubicka S , et al; AIO Colorectal Study Group. Phase III study of capecitabine plus oxaliplatin compared with fluorouracil and leucovorin plus oxaliplatin in metastatic colorectal cancer: a final report of the AIO Colorectal Study Group. J Clin Oncol 2007; 25 (27) 4217-4223
- 24 Kim ST, Lee J, Park SH , et al. Clinical impact of microsatellite instability in colon cancer following adjuvant FOLFOX therapy. Cancer Chemother Pharmacol 2010; 66 (4) 659-667
- 25 Bertagnolli MM, Niedzwiecki D, Compton CC , et al. Microsatellite instability predicts improved response to adjuvant therapy with irinotecan, fluorouracil, and leucovorin in stage III colon cancer: Cancer and Leukemia Group B Protocol 89803. J Clin Oncol 2009; 27 (11) 1814-1821
- 26 Bendardaf R, Lamlum H, Ristamäki R, Korkeila E, Syrjänen K, Pyrhönen S. Mismatch repair status is a predictive factor of tumour response to 5-fluorouracil and irinotecan chemotherapy in patients with advanced colorectal cancer. Tumour Biol 2007; 28 (4) 212-220
- 27 Kim JE, Hong YS, Ryu MH , et al. Association between deficient mismatch repair system and efficacy to irinotecan-containing chemotherapy in metastatic colon cancer. Cancer Sci 2011; 102 (9) 1706-1711