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. 2015 Jun;15(3):219-25.
doi: 10.1038/tpj.2014.64. Epub 2014 Oct 21.

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

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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

E Cecchin et al. Pharmacogenomics J. .

Abstract

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.

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