Folate intake along with genetic polymorphisms in methylenetetrahydrofolate reductase and thymidylate synthase in patients with advanced gastric cancer.

Abstract

BACKGROUND:

A relationship between dietary folate intake and efficacy of fluorouracil (FU) is supported by preclinical data. Furthermore, there are several reports that evaluated genetic polymorphisms of MTHFR (methylenetetrahydrofolate reductase) or TYMS (thymidylate synthase) and efficacy of FU. However, to our knowledge, there are no reports that evaluate simultaneously the effects of folate intake and genetic polymorphisms on clinical outcome of gastric cancer patients.

METHODS:

We retrospectively analyzed the survival impact of estimated folate intake by a food frequency questionnaire and MTHFR and TYMS polymorphisms in 132 patients with advanced gastric cancer who were treated with first-line FU-based chemotherapy.

RESULTS:

Median overall survival was 11.3 months (95% confidence interval, 9.4-13.4 mo) and median progression-free survival was 5.2 months (95% confidence interval, 4.1-6.3 mo). Patients with folate intake of >260 microg/day (n=88) showed longer overall survival compared with low folate intake (n=44; overall survival, 12.2 versus 8.4 mo). In a multivariate Cox model, patients who had folate intake of >260 microg/day, MTHFR 677 TT polymorphism, and TYMS-3' untranslated region 6-bp insertion were associated with better survival. Similar tendency was observed in progression-free survival. No interaction was observed between folate intake and favorable genotypes.

CONCLUSION:

Folate intake and genetic polymorphisms of MTHFR and TYMS were associated with better clinical outcome by FU-based chemotherapy in advanced gastric cancer.

IMPACT:

Our results suggested folate intake and folate-related genetic polymorphisms may play an important role in efficacy of FU-based chemotherapy in advanced gastric cancer.

• Authors: Kohei Shitara, Kei Muro, Seiji Ito, Akira Sawaki, Masahiro Tajika, Hiroki Kawai, Tomoya Yokota, Daisuke Takahari, Takashi Shibata, Takashi Ura, Hidemi Ito, Satoyo Hosono, Takakazu Kawase, Miki Watanabe, Kazuo Tajima, Yasushi Yatabe, Hideo Tanaka, Keitaro Matsuo
• Journal: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology (Cancer Epidemiol Biomarkers Prev) Vol. 19 Issue 5 Pg. 1311-9 (May 2010) ISSN: 1538-7755 [Electronic] United States
• PMID: 20447923 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright (c) 2010 AACR

Chemical References

• Folic Acid
• Methylenetetrahydrofolate Reductase (NADPH2)
• Thymidylate Synthase

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Cohort Studies
• Female
• Folic Acid (administration & dosage)
• Humans
• Male
• Methylenetetrahydrofolate Reductase (NADPH2) (genetics)
• Middle Aged
• Polymorphism, Genetic
• Retrospective Studies
• Stomach Neoplasms (drug therapy, genetics, pathology)
• Survival Rate
• Thymidylate Synthase (genetics)
• Treatment Outcome