MTHFR polymorphisms and 5-FU-based adjuvant chemotherapy in colorectal cancer

Shoaib Afzal; S. A. Jensen; B. Veiner; Ulla Vogel; J. P. Matsen; J. B. Sørensen; P. K. Andersen; H. E. Poulsen

doi:10.1093/annonc/mdp046

MTHFR polymorphisms and 5-FU-based adjuvant chemotherapy in colorectal cancer

Shoaib Afzal, S. A. Jensen, B. Veiner, Ulla Vogel, J. P. Matsen, J. B. Sørensen, P. K. Andersen, H. E. Poulsen

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

Abstract

Patients and methods: We included 331 patients who had been treated with adjuvant 5-FU/leucovorin chemotherapy after intended curative resection between 1997 and 2003. Clinical data, including relapse rates, overall survival, and tumor stage, were collected. DNA was extracted from formalin-fixed tumor tissue and analyzed for the MTHFR 677C > T and 1298A > C SNPs with real-time PCR.

Results: The MTHFR 677C > T and 1298A > C polymorphisms were not associated with survival or relapse-free survival (P > 0.2). The 677 CC genotype was associated to toxicity (odds ratio = 1.83, P = 0.01).

Conclusions: The MTHFR 677C > T and 1298A > C polymorphisms probably do not predict efficacy of adjuvant 5-FU treatment in colorectal cancer after complete resection; however, the 677C > T polymorphism may be associated with lower toxicity in 5-FU treatment. Implementation of SNP analysis for these polymorphisms for individualized treatment is premature.

Originalsprog	Engelsk
Tidsskrift	Annals of Oncology
Vol/bind	20
Udgave nummer	10
Sider (fra-til)	1660-1666
ISSN	0923-7534
DOI	https://doi.org/10.1093/annonc/mdp046
Status	Udgivet - 2009

Link til dokument

10.1093/annonc/mdp046

Citer dette

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title = "MTHFR polymorphisms and 5-FU-based adjuvant chemotherapy in colorectal cancer",

abstract = "Patients and methods: We included 331 patients who had been treated with adjuvant 5-FU/leucovorin chemotherapy after intended curative resection between 1997 and 2003. Clinical data, including relapse rates, overall survival, and tumor stage, were collected. DNA was extracted from formalin-fixed tumor tissue and analyzed for the MTHFR 677C > T and 1298A > C SNPs with real-time PCR. Results: The MTHFR 677C > T and 1298A > C polymorphisms were not associated with survival or relapse-free survival (P > 0.2). The 677 CC genotype was associated to toxicity (odds ratio = 1.83, P = 0.01).Conclusions: The MTHFR 677C > T and 1298A > C polymorphisms probably do not predict efficacy of adjuvant 5-FU treatment in colorectal cancer after complete resection; however, the 677C > T polymorphism may be associated with lower toxicity in 5-FU treatment. Implementation of SNP analysis for these polymorphisms for individualized treatment is premature.",

keywords = "colorectal cancer, 5-fluorouracil, methylenetetrahydrofolate reductase, pharmacogenetics, single-nucleotide polymorphisms",

author = "Shoaib Afzal and Jensen, {S. A.} and B. Veiner and Ulla Vogel and Matsen, {J. P.} and S{\o}rensen, {J. B.} and Andersen, {P. K.} and Poulsen, {H. E.}",

year = "2009",

doi = "10.1093/annonc/mdp046",

language = "English",

volume = "20",

pages = "1660--1666",

journal = "Annals of Oncology",

issn = "0923-7534",

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TY - JOUR

T1 - MTHFR polymorphisms and 5-FU-based adjuvant chemotherapy in colorectal cancer

AU - Afzal, Shoaib

AU - Jensen, S. A.

AU - Veiner, B.

AU - Vogel, Ulla

AU - Matsen, J. P.

AU - Sørensen, J. B.

AU - Andersen, P. K.

AU - Poulsen, H. E.

PY - 2009

Y1 - 2009

N2 - Patients and methods: We included 331 patients who had been treated with adjuvant 5-FU/leucovorin chemotherapy after intended curative resection between 1997 and 2003. Clinical data, including relapse rates, overall survival, and tumor stage, were collected. DNA was extracted from formalin-fixed tumor tissue and analyzed for the MTHFR 677C > T and 1298A > C SNPs with real-time PCR. Results: The MTHFR 677C > T and 1298A > C polymorphisms were not associated with survival or relapse-free survival (P > 0.2). The 677 CC genotype was associated to toxicity (odds ratio = 1.83, P = 0.01).Conclusions: The MTHFR 677C > T and 1298A > C polymorphisms probably do not predict efficacy of adjuvant 5-FU treatment in colorectal cancer after complete resection; however, the 677C > T polymorphism may be associated with lower toxicity in 5-FU treatment. Implementation of SNP analysis for these polymorphisms for individualized treatment is premature.

AB - Patients and methods: We included 331 patients who had been treated with adjuvant 5-FU/leucovorin chemotherapy after intended curative resection between 1997 and 2003. Clinical data, including relapse rates, overall survival, and tumor stage, were collected. DNA was extracted from formalin-fixed tumor tissue and analyzed for the MTHFR 677C > T and 1298A > C SNPs with real-time PCR. Results: The MTHFR 677C > T and 1298A > C polymorphisms were not associated with survival or relapse-free survival (P > 0.2). The 677 CC genotype was associated to toxicity (odds ratio = 1.83, P = 0.01).Conclusions: The MTHFR 677C > T and 1298A > C polymorphisms probably do not predict efficacy of adjuvant 5-FU treatment in colorectal cancer after complete resection; however, the 677C > T polymorphism may be associated with lower toxicity in 5-FU treatment. Implementation of SNP analysis for these polymorphisms for individualized treatment is premature.

KW - colorectal cancer

KW - 5-fluorouracil

KW - methylenetetrahydrofolate reductase

KW - pharmacogenetics

KW - single-nucleotide polymorphisms

U2 - 10.1093/annonc/mdp046

DO - 10.1093/annonc/mdp046

M3 - Journal article

SN - 0923-7534

VL - 20

SP - 1660

EP - 1666

JO - Annals of Oncology

JF - Annals of Oncology

IS - 10

ER -