Polymorphisms of folate metabolism-related genes and survival of patients with colorectal cancer in the Korean population.

Abstract

BACKGROUND:

5-Fluorouracil (5-FU) is a cornerstone of chemotherapy for colorectal cancer (CRC), and the major targets of 5-FU are thymidylate synthase (TS), methylenetetrahydrofolate reductase (MTHFR), and reduced folate carrier 1 (RFC1). We hypothesized that polymorphisms in the genes encoding these proteins would be associated with CRC patient survival.

PATIENTS AND METHODS:

We genotyped the following polymorphisms in 372 CRC patients: TS enhancer region (TSER), TS 1494del6, MTHFR 677C>T and 1298A>C, and RFC1 -43T>C, 80G>A, and 696C>T. Using Kaplan-Meier curves, log-rank tests, and Cox proportional hazard models, we evaluated associations between these polymorphisms and overall survival (OS).

RESULTS:

The combined TS 1494 0bp6bp+6bp6bp genotype was associated with reduced OS compared to the TS 1494 0bp0bp genotype. Among rectal cancer patients, the RFC1 -43CC and 80AA genotypes were associated with favorable OS.

CONCLUSIONS:

Our data suggest that TS and RFC1 polymorphisms are associated with CRC prognosis in Korean patients. Further studies are needed to verify these findings.

• Authors: Moon Ju Jang, Jong Woo Kim, Young Joo Jeon, So Young Chong, Sung Pyo Hong, Seong Gyu Hwang, Doyeun Oh, Yun Kyung Cho, Young Geon Ji, Nam Keun Kim
• Journal: Gene (Gene) Vol. 533 Issue 2 Pg. 558-64 (Jan 10 2014) ISSN: 1879-0038 [Electronic] Netherlands
• PMID: 24100087 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2013 Elsevier B.V. All rights reserved.

Chemical References

• Reduced Folate Carrier Protein
• SLC19A1 protein, human
• Folic Acid
• MTHFR protein, human
• Methylenetetrahydrofolate Reductase (NADPH2)
• Thymidylate Synthase
• Fluorouracil

Topics

• Aged
• Asian People (genetics)
• Colorectal Neoplasms (drug therapy, genetics, mortality)
• Female
• Fluorouracil (pharmacokinetics, therapeutic use)
• Folic Acid (metabolism)
• Humans
• Male
• Metabolic Networks and Pathways (genetics)
• Methylenetetrahydrofolate Reductase (NADPH2) (genetics)
• Middle Aged
• Polymorphism, Genetic
• Population (genetics)
• Reduced Folate Carrier Protein (genetics)
• Republic of Korea (epidemiology)
• Survival Analysis
• Thymidylate Synthase (genetics)