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

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

研究成果: Article査読

27 被引用数 (Scopus)

抄録

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 μg/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 μg/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.

本文言語English
ページ(範囲)1311-1319
ページ数9
ジャーナルCancer Epidemiology Biomarkers and Prevention
19
5
DOI
出版ステータスPublished - 05-2010
外部発表はい

All Science Journal Classification (ASJC) codes

  • 疫学
  • 腫瘍学

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