Open Journal Systems

KRAS as a prognostic marker for metastatic colorectal cancer: Qatar experience

Kakil I Rasul ()
Hind Elmalik ()
Mini Satheesh ()
Prem Chandra ()


Colorectal cancer (CRC) is the third most common cancer worldwide and in Qatar. Kirsten Ras (KRAS) mutation occurs in 30%–50% of CRC cases in different geographical areas. A total of 104 metastatic CRC cases were tested for KRAS mutation from 2009–2013 at the National Center for Cancer Care and Research (NCCR), Qatar. The incidence of KRAS mutation was 42% versus that of the wild-type (58%). Wild-type KRAS metastatic CRC (mCRC) patients tend to have better survival and this was especially evident after they received anti-epithelial growth factor receptors targeted therapy. Meanwhile, mutant-type KRAS mCRC patients receiving anti-vascular endothelial growth factor were more inclined to have poor survival outcomes. To confirm the observation, more studies with larger sample populations and a longer follow-up duration are needed. To our best knowledge, this is the first known report of KRAS status and its impact on the prognosis of metastatic colorectal cancer.


colorectal cancer; chemotherapy; KRAS; anti-EGFR; anti-VEGF

Full Text:



ESMO Clinical Practice Guidelines, Volume 21, 2010.

Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics 2002. CA Cancer J Clin 2005; 55(2): 74–108. doi: 10.3322/canjclin.55.2.74.

Kim ST, Park KH, Kim JS, Shin SW, Kim YH. Impact of KRAS mutation status on outcomes in metastatic colon cancer patients without anti-epidermal growth factor receptor therapy. Cancer Res Treat 2013; 45(1): 55–62. doi: 10.4143/crt.2013.45.1.55.

Vogelstein B, Fearon ER, Hamilton SR, Kern SE, Preisinger AC, Leppert M, Smits AMM, Bos JL. Genetic alterations during colorectal-tumor development. N Engl J Med 1988; 319: 525–532. doi: 10.1056/NEJM198809013190901.

Hamelin R, Laurent-Puig P, Olschwang S, Jego N, Asselain B, Remvikos Y, Girodet J, Salmon RJ, Thomas G. Association of p53 mutations with short survival in colorectal cancer. Gastroenterology 1994; 106(1): 42–48.

Ahnen DJ, Feigl P, Quan G, Fenoglio-Preiser C, Lovato LC, Bunn PA Jr, Stemmerman G, Wells JD, Macdonald JS, Meyskens FL Jr. Ki-ras mutation and p53 overexpression predict the clinical behavior of colorectal cancer: A Southwest oncology group study. Cancer Res 1998; 58(6): 1149–1158.

Schubbert S, Shannon K, Bollag G. Hyperactive Ras in developmental disorders and cancer. Nat Rev Cancer 2007; 7: 295–308. doi: 10.1038/nrc2109.

Harrari PM. Epidermal growth factor receptor inhibition strategies in oncology. Endocr Relat Cancer 2004; 11: 689–708. doi: 10.1677/erc.1.00600.

Kiaris H, Spandidos DA. Mutations of ras genes in human tumors (review). Int J Oncol 1995; 7(3): 413–421. doi: 10.3892/ijo.7.3.413.

Douillard JY, Siena S, Cassidy J, Tabernero J, Burkes R, Barugel M, Humblet Y, Bodoky G, Cunningham D, Jassem J, Rivera F, Kocákova I, Ruff P, Błasińska-Morawiec M, Šmakal M, Canon JL, Rother M, Oliner KS, Tian Y, Xu F, Sidhu R. Randomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FO-LFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: The PRIME study. J Clin Oncol 2010; 28(31): 4697–4705. doi:10.1200/JCO.2009.27.4860.

Cancer Care Ontario (CCO) [Internet]. Toronto (ON): CCO; 2011 [cited June 27, 2011]. Available from: (search for the CETU or PNTM chemotherapy regimen).

BC Cancer Agency (BCCA) [Internet]. Vancouver (BC): BCCA; 2010 cited June 27, 2011]. Available from: (see the GIAVCETIR or GIAVPANI protocol).

Aubin F, Gill S, Burkes R, Colwell B, Kamel-Reid S, Koski S, Pollett A, Samson B, Tehfe M, Wong R, Young S, Soulières D. Canadian expert group consensus recommendations: KRAS testing in colorectal cancer. Curr Oncol 2011; 18(4): 180–184. doi: 10.3747/co.v18i4.779.

Peeters M, Douillard JY, Van Cutsem E, Siena S, Zhang K, Williams R, Wiezorek J. Mutant KRAS codon 12 and 13 alleles in patients with metastatic colorectal cancer: Assessment as prognostic and predictive biomarkers of response to panitumumab. J Clin Oncol 2013; 31: 759765. doi: 10.1200/JCO.2012.45.1492.

de Gramont A, Figer A, Seymour M, Homerin M, Hmissi A, Cassidy J, Boni C, Cortes-Funes H, Cervantes A, Freyer G, Papamichael D, Le Bail N, Louvet C, Hendler D, de Braud F, Wilson C, Morvan F, Bonetti A. Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol 2000; 18(16): 2938–2947.

Douillard JY, Cunningham D, Roth AD, Navarro M, James RD, Karasek P, Jandik P, Iveson T, Carmichael J, Alakl M, Gruia G, Awad L, Rougier P. Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: A multicentre randomised trial. Lancet 2000; 355(9209): 1041–1047. doi: 10.1016/S0140-6736(00)02034-1.

Goldberg RM, Sargent DJ, Morton RF, Fuchs CS, Ramanathan RK, Williamson SK, Findlay BP, Pitot HC, Alberts SR. A randomized controlled trial of fluorouracil plus leucovorin, irinotecan, and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancer. J Clin Oncol 2004; 22(1): 23–30. doi: 10.1200/JCO.2004.09.046.

Saltz LB, Cox JV, Blanke C, Rosen LS, Fehrenbacher L, Moore MJ, Maroun JA, Ackland SP, Locker PK, Pirotta N, Elfring GL, Miller LL. Irinotecan plus fluorouracil and leucovorin for metastatic colorectal cancer. N Engl J Med 2000; 343: 905–914. doi: 10.1056/NEJM200009283431302.

Lièvre A, Bachet JB, Boige V, Cayre A, Le Corre D, Buc E, Ychou M, Bouché O, Landi B, Louvet C, André T, Bibeau F, Diebold MD, Rougier P, Ducreux M, Tomasic G, Emile JF, Penault-Llorca F, Laurent-Puig P. KRAS mutations as an independent prognostic factor in patients with advanced colorectal cancer treated with cetuximab. J Clin Oncol 2008; 26(15): 374–379. doi: 10.1200/JCO.2007.12.5906.

Andreyev HJN, Norman AR, Clarke PA, Cunningham D, Oates JR. Kirsten ras mutations in patients with colorectal cancer: The multicenter “RASCAL” study. J Natl Cancer Inst 1998; 90(9): 675–684. doi: 10.1093/jnci/90.9.675.

Van Cutsem E, Köhne CH, Hitre E, Zaluski J, Chang Chien CR, Makhson A, D'Haens G, Pintér T, Lim R, Bodoky G, Roh JK, Folprecht G, Ruff P, Stroh C, Tejpar S, Schlichting M, Nippgen J, Rougier P. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med 2009; 360: 1408–1417. doi: 10.1056/NEJMoa¬0805019.

Anwar S, Frayling IM, Scott NA, Carlson GL. Systematic review of genetic influences on the prognosis of colorectal cancer. Br J Surg 2004; 91(10): 1275–1291. doi: 10.1002/bjs.4737.

Locker GY, Hamilton S, Harris J, Jessup JM, Kemeny N, Macdonald JS, Somerfield MR, Hayes DF, Bast RC Jr. ASCO 2006 update of recommendations for the use of tumor markers in gastrointestinal cancer. J Clin Oncol 2006; 24(33): 5313–5327. doi: 10.1200/JCO.2006.08.2644.

Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, Berlin J, Baron A, Griffing S, Holmgren E, Ferrara N, Fyfe G, Rogers B, Ross R, Kabbinavar F. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 2004; 350: 2335–2342. doi: 10.1056/NEJMoa032691.



  • There are currently no refbacks.

Copyright (c) 2018 Kakil I Rasul, Hind Elmalik, Mini Satheesh, Prem Chandra

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.