MTHFR-1298 A > C (rs1801131) is a predictor of survival in two cohorts of stage II/III colorectal cancer patients treated with adjuvant fluoropyrimidine chemotherapy with or without oxaliplatin

被引：15
作者：
Cecchin, E. [1 ]
Perrone, G. [2 ]
Nobili, S. [2 ]
Polesel, J. [3 ]
De Mattia, E. [1 ]
Zanusso, C. [1 ]
Petreni, P. [2 ]
Lonardi, S. [4 ]
Pella, N. [5 ]
D'Andrea, M. [6 ]
Errante, D. [7 ]
Rizzolio, F. [1 ]
Mazzei, T. [2 ]
Landini, I. [2 ]
Mini, E. [8 ]
Toffoli, G. [1 ]
机构：
[1] Ctr Riferimento Oncol, Natl Canc Inst, Expt & Clin Pharmacol, I-33081 Aviano, Italy
[2] Univ Florence, Dept Hlth Sci, Sect Clin Pharmacol & Oncol, Florence, Italy
[3] Ctr Riferimento Oncol, Natl Canc Inst, Epidemiol & Biostat Unit, I-33081 Aviano, Italy
[4] Ist Oncol Veneto, IRCCS, Med Oncol Unit 1, Padua, Italy
[5] Univ Hosp, Med Oncol Unit, Udine, Italy
[6] San Filippo Neri Hosp, Med Oncol Unit, Rome, Italy
[7] Osped Civile Vittorio Veneto, Med Oncol Unit, Veneto, TV, Italy
[8] Univ Florence, Dept Expt & Clin Med, Sect Internal Med, Florence, Italy
来源：
PHARMACOGENOMICS JOURNAL | 2015年 / 15卷 / 03期
基金：
欧洲研究理事会;
关键词：
METHYLENETETRAHYDROFOLATE REDUCTASE GENE; III COLON-CANCER; THYMIDYLATE-SYNTHASE; IRINOTECAN-PHARMACOKINETICS; MICROSATELLITE INSTABILITY; GENOMIC PREDICTORS; FOLATE INTAKE; POLYMORPHISMS; FLUOROURACIL; ASSOCIATION;
D O I：
10.1038/tpj.2014.64
中图分类号：
Q3 [遗传学];
学科分类号：
071007 ; 090102 ;
摘要：
Adjuvant treatment based on fluoropyrimidines (FL) improves the prognosis of stage II/III colorectal cancer (CRC). Validated predictive/prognostic biomarkers would spare therapy-related morbidity in patients with a good prognosis. We compared the impact of a set of 22 FL-related polymorphisms with the prognosis of two cohorts of CRC patients treated with adjuvant FL with or without OXA, including a total of 262 cases. 5,10-Methylentetrahydrofolate reductase (MTHFR) MTHFR-1298 A > C (rs1801131) polymorphism had a concordant effect: MTHFR-rs1801131-1298CC genotype carriers had a worse disease free survival (DFS) in both the cohorts. In the pooled population MTHFR-rs1801131-1298CC carriers had also a worse overall survival. We computed a clinical score related to DFS including MTHFR-rs1801131, tumor stage, sex and tumor location, where rs1801131 is the most detrimental factor (hazard ratio = 5.3, 95% confidence interval = 2.2-12.9; P-value = 0.0006). MTHFR-rs1801131 is a prognostic factor that could be used as an additional criteria for the choice of the proper adjuvant regimen in stage II/III colorectal cancer patients.
引用
收藏
页码：219 / 225
页数：7
相关论文
共 39 条
[1]   MTHFR polymorphisms and 5-FU-based adjuvant chemotherapy in colorectal cancer [J].
Afzal, S. ;
Jensen, S. A. ;
Vainer, B. ;
Vogel, U. ;
Matsen, J. P. ;
Sorensen, J. B. ;
Andersen, P. K. ;
Poulsen, H. E. .
ANNALS OF ONCOLOGY, 2009, 20 (10) :1660-1666
[2]   Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer [J].
Andre, T ;
Boni, C ;
Mounedji-Boudiaf, L ;
Navarro, M ;
Tabernero, J ;
Hickish, T ;
Topham, C ;
Zaninelli, M ;
Clingan, P ;
Bridgewater, J ;
Tabah-Fisch, I ;
de Gramont, A .
NEW ENGLAND JOURNAL OF MEDICINE, 2004, 350 (23) :2343-2351
[3]   Improved Overall Survival With Oxaliplatin, Fluorouracil, and Leucovorin As Adjuvant Treatment in Stage II or III Colon Cancer in the MOSAIC Trial [J].
Andre, Thierry ;
Boni, Corrado ;
Navarro, Matilde ;
Tabernero, Josep ;
Hickish, Tamas ;
Topham, Clare ;
Bonetti, Andrea ;
Clingan, Philip ;
Bridgewater, John ;
Rivera, Fernando ;
de Gramont, Aimery .
JOURNAL OF CLINICAL ONCOLOGY, 2009, 27 (19) :3109-3116
[4]   Pharmacogenetic Assessment of Toxicity and Outcome in Patients With Metastatic Colorectal Cancer Treated With LV5FU2, FOLFOX, and FOLFIRI: FFCD 2000-05 [J].
Boige, Valerie ;
Mendiboure, Jean ;
Pignon, Jean-Pierre ;
Loriot, Marie-Anne ;
Castaing, Marine ;
Barrois, Michel ;
Malka, David ;
Tregouet, David-Alexandre ;
Bouche, Olivier ;
Le Corre, Delphine ;
Miran, Isabelle ;
Mulot, Claire ;
Ducreux, Michel ;
Beaune, Philippe ;
Laurent-Puig, Pierre .
JOURNAL OF CLINICAL ONCOLOGY, 2010, 28 (15) :2556-2564
[5]   The influence of fluorouracil outcome parameters on tolerance and efficacy in patients with advanced colorectal cancer [J].
Capitain, O. ;
Boisdron-Celle, M. ;
Poirier, A-L ;
Abadie-Lacourtoisie, S. ;
Morel, A. ;
Gamelin, E. .
PHARMACOGENOMICS JOURNAL, 2008, 8 (04) :256-267
[6]   A prospective validation pharmacogenomic study in the adjuvant setting of colorectal cancer patients treated with the 5-fluorouracil/leucovorin/oxaliplatin (FOLFOX4) regimen [J].
Cecchin, E. ;
D'Andrea, M. ;
Lonardi, S. ;
Zanusso, C. ;
Pella, N. ;
Errante, D. ;
De Mattia, E. ;
Polesel, J. ;
Innocenti, F. ;
Toffoli, G. .
PHARMACOGENOMICS JOURNAL, 2013, 13 (05) :403-409
[7]   5,10-methylenetetrahydrofolate reductase 677 and 1298 polymorphisms, folate intake, and microsatellite instability in colon cancer [J].
Eaton, AM ;
Sandler, R ;
Carethers, JM ;
Millikan, RC ;
Galanko, J ;
Keku, TO .
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION, 2005, 14 (08) :2023-2029
[8]   Thymidylate synthase and methylenetetrahydrofolate reductase gene polymorphisms: relationships with 5-fluorouracil sensitivity [J].
Etienne, MC ;
Ilc, K ;
Formento, JL ;
Laurent-Puig, P ;
Formento, P ;
Cheradame, S ;
Fischel, JL ;
Milano, G .
BRITISH JOURNAL OF CANCER, 2004, 90 (02) :526-534
[9]   Methylenetetrahydrofolate reductase gene polymorphisms and response to fluorouracil-based treatment in advanced colorectal cancer patients [J].
Etienne, MC ;
Formento, JL ;
Chazal, M ;
Francoual, M ;
Magné, N ;
Formento, P ;
Bourgeon, A ;
Seitz, JF ;
Delpero, JR ;
Letoublon, C ;
Pezet, D ;
Milano, G .
PHARMACOGENETICS, 2004, 14 (12) :785-792
[10]   Association of polymorphisms MTHFR C677T and A1298C with risk of colorectal cancer, genetic and epigenetic characteristic of tumors, and response to chemotherapy [J].
Fernandez-Peralta, Antonia M. ;
Daimiel, Lydia ;
Nejda, Nargisse ;
Iglesias, Daniel ;
Medina Arana, Vicente ;
Gonzalez-Aguilera, Juan J. .
INTERNATIONAL JOURNAL OF COLORECTAL DISEASE, 2010, 25 (02) :141-151
1234