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.
| Original language | English |
|---|---|
| Pages (from-to) | 219-225 |
| Number of pages | 7 |
| Journal | Pharmacogenomics Journal |
| Volume | 15 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Jun 26 2015 |
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ASJC Scopus subject areas
- Pharmacology
- Molecular Medicine
- Genetics
- Medicine(all)
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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. / Cecchin, E.; Perrone, G.; Nobili, S.; Polesel, J.; De Mattia, E.; Zanusso, C.; Petreni, P.; Lonardi, S.; Pella, N.; D'Andrea, M.; Errante, D.; Rizzolio, F.; Mazzei, T.; Landini, I.; Mini, E.; Toffoli, G.
In: Pharmacogenomics Journal, Vol. 15, No. 3, 26.06.2015, p. 219-225.Research output: Contribution to journal › Article
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TY - JOUR
T1 - 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
AU - Cecchin, E.
AU - Perrone, G.
AU - Nobili, S.
AU - Polesel, J.
AU - De Mattia, E.
AU - Zanusso, C.
AU - Petreni, P.
AU - Lonardi, S.
AU - Pella, N.
AU - D'Andrea, M.
AU - Errante, D.
AU - Rizzolio, F.
AU - Mazzei, T.
AU - Landini, I.
AU - Mini, E.
AU - Toffoli, G.
PY - 2015/6/26
Y1 - 2015/6/26
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84929952032&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84929952032&partnerID=8YFLogxK
U2 - 10.1038/tpj.2014.64
DO - 10.1038/tpj.2014.64
M3 - Article
C2 - 25331073
AN - SCOPUS:84929952032
VL - 15
SP - 219
EP - 225
JO - Pharmacogenomics Journal
JF - Pharmacogenomics Journal
SN - 1470-269X
IS - 3
ER -