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


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


CONCLUSIONS
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.
Shitara
Kohei
K
Department of Clinical Oncology, Aichi Cancer Center Hospital, and Department of Epidemiology, Nagoya University Graduate School of Medicine, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Aichi, Japan. Kouheis0824@yahoo.co.jp
Muro
Kei
K
Ito
Seiji
S
Sawaki
Akira
A
Tajika
Masahiro
M
Kawai
Hiroki
H
Yokota
Tomoya
T
Takahari
Daisuke
D
Shibata
Takashi
T
Ura
Takashi
T
Ito
Hidemi
H
Hosono
Satoyo
S
Kawase
Takakazu
T
Watanabe
Miki
M
Tajima
Kazuo
K
Yatabe
Yasushi
Y
Tanaka
Hideo
H
Matsuo
Keitaro
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015331:Cohort Studies; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012189:Retrospective Studies; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D015996:Survival Rate; D013940:Thymidylate Synthase / Q000235:genetics*; D016896:Treatment Outcome
D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013940:Thymidylate Synthase