The association of polymorphisms in folate-metabolizing genes with response to adjuvant chemotherapy of colorectal cancer

The association of polymorphisms in folate-metabolizing genes with response to adjuvant... Background Colorectal cancer (CRC) is one of the major health issues worldwide. 5-Fluorouracil (5-FU) is a cornerstone of chemotherapy for CRC and the major targets of 5-FU are folate-metabolizing enzymes. Methods A total of 103 CRC patients with complete clinical data were included in this prospective cohort study. Genotyp- ing was performed using polymerase chain reaction (PCR) followed by sequencing. Using Kaplan–Meier curves, log-rank tests, and Cox proportional hazard models, we evaluated associations between functional polymorphisms in four genes MTHFR (1298A>C and 677C>T), DPYD (496A>G and 85T>C), DHFR 19 bp del, and MTR (2756 A>G) with disease- free survival (DFS). Results The minor allele frequencies of MTHFR 1298A>C, MTHFR 677C>T, DPYD 496A>G, DPYD 85T>C, DHFR 19 bp del, and MTR 2756 A>G were 0.364, 0.214, 0.116, 0.209, 0.383, and 0.097, respectively. CRC patients carrying the homozygous GG genotype in DPYD 496A>G had 4.36 times shorter DFS than wild-type AA carriers, (DFS vs : 8.0 ± 4 GG AA vs 69.0 ± 10 months; HR 4.36, 95% CI 1.04–18; p = 0.04). Moreover, female carriers of homozygous CC genotype of DPYD 85T>C had shorter DFS compared to either heterozygous or wild-type genotypes, and were 12.7 times shorter than wild- type TT carriers (DFS http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Cancer Chemotherapy and Pharmacology Springer Journals

The association of polymorphisms in folate-metabolizing genes with response to adjuvant chemotherapy of colorectal cancer

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Publisher
Springer Berlin Heidelberg
Copyright
Copyright © 2018 by Springer-Verlag GmbH Germany, part of Springer Nature
Subject
Medicine & Public Health; Oncology; Pharmacology/Toxicology; Cancer Research
ISSN
0344-5704
eISSN
1432-0843
D.O.I.
10.1007/s00280-018-3608-6
Publisher site
See Article on Publisher Site

Abstract

Background Colorectal cancer (CRC) is one of the major health issues worldwide. 5-Fluorouracil (5-FU) is a cornerstone of chemotherapy for CRC and the major targets of 5-FU are folate-metabolizing enzymes. Methods A total of 103 CRC patients with complete clinical data were included in this prospective cohort study. Genotyp- ing was performed using polymerase chain reaction (PCR) followed by sequencing. Using Kaplan–Meier curves, log-rank tests, and Cox proportional hazard models, we evaluated associations between functional polymorphisms in four genes MTHFR (1298A>C and 677C>T), DPYD (496A>G and 85T>C), DHFR 19 bp del, and MTR (2756 A>G) with disease- free survival (DFS). Results The minor allele frequencies of MTHFR 1298A>C, MTHFR 677C>T, DPYD 496A>G, DPYD 85T>C, DHFR 19 bp del, and MTR 2756 A>G were 0.364, 0.214, 0.116, 0.209, 0.383, and 0.097, respectively. CRC patients carrying the homozygous GG genotype in DPYD 496A>G had 4.36 times shorter DFS than wild-type AA carriers, (DFS vs : 8.0 ± 4 GG AA vs 69.0 ± 10 months; HR 4.36, 95% CI 1.04–18; p = 0.04). Moreover, female carriers of homozygous CC genotype of DPYD 85T>C had shorter DFS compared to either heterozygous or wild-type genotypes, and were 12.7 times shorter than wild- type TT carriers (DFS

Journal

Cancer Chemotherapy and PharmacologySpringer Journals

Published: May 29, 2018

References

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