title: Lower serum folate is associated with development and invasiveness of gastric cancer.
abstract: OBJECTIVE
  To evaluate the associations of serum folate level with development, invasiveness and patient survival of gastric cancer.
  
  
  METHODS
  In this nested case-control study, patients with newly diagnosed gastric cancer undergoing gastrectomy were enrolled, and patients receiving chemotherapy prior to surgery, with other concurrent malignancy, or of the aboriginal and alien populations were excluded. In total, 155 gastric cancer patients and 149 healthy controls were enrolled for determination of serum folate levels and their correlation with gastric cancer. Using the median value of serum folate computed among the overall population as the cutoff value, the associations between serum folate and gastric cancer in all cases and different age and gender subgroups were analyzed by multivariate logistic regression analysis. In the patient cohort of gastric cancer, receiver-operating characteristic analyses were performed to calculate the best cutoff values of serum folate, and the associations between serum folate levels and clinicopathological features were further analyzed by multivariate regression analysis. Survival analyses were conducted using the Cox proportional hazards model.
  
  
  RESULTS
  The mean serum folate level was significantly lower in gastric cancer patients than that in controls (3.71 ± 0.30 ng/mL vs 8.00 ± 0.54 ng/mL, P < 0.01), and folate levels were consistently lower in gastric cancer patients regardless of age and gender (all P < 0.01). Using the median serum folate value as the cutoff value, low serum folate was significantly associated with gastric cancer risk in the whole population (OR = 19.77, 95%CI: 10.54-37.06, P < 0.001) and all strata (age < 60 years OR = 17.39, 95%CI: 7.28-41.54, age ≥ 60 years (OR = 21.67, 95%CI: 8.27-56.80), males (OR = 17.95, 95%CI: 7.93-40.62), and females (OR = 20.95, 95%CI: 7.66-57.31); all P < 0.001. In the patient cohort of gastric cancer, the respective cutoff values showed that low serum folate levels were significantly associated with serosal invasion (OR = 2.54, 95%CI: 1.23-5.23), lymphatic invasion (OR = 2.23, 95%CI: 1.17-4.26), and liver metastasis (OR = 6.67, 95%CI: 1.28-34.91) of gastric cancer (all P < 0.05). Serum folate level below 1.90 ng/mL was associated with poor patient survival (HR = 1.84, 95%CI: 1.04-3.27, P < 0.05) in univariate analysis.
  
  
  CONCLUSIONS
  Lower serum folate levels were significantly associated with gastric cancer development and invasive phenotypes. The role of folate depletion in gastric cancer invasion warrants further study.
authors.affiliation: Teng-Yu Lee, Hsien-Yuan Lane, Chun-Ying Wu, Graduate Institute of Clinical Medical Science, China Medical University, Taichung 407, Taiwan.
authors.forename: Teng-Yu
authors.initials: TY
authors.lastname: Lee
authors.affiliation: Teng-Yu Lee, Hsien-Yuan Lane, Chun-Ying Wu, Graduate Institute of Clinical Medical Science, China Medical University, Taichung 407, Taiwan.
authors.forename: En-Pei
authors.initials: EP
authors.lastname: Chiang
authors.affiliation: Teng-Yu Lee, Hsien-Yuan Lane, Chun-Ying Wu, Graduate Institute of Clinical Medical Science, China Medical University, Taichung 407, Taiwan.
authors.forename: Yin-Ting
authors.initials: YT
authors.lastname: Shih
authors.affiliation: Teng-Yu Lee, Hsien-Yuan Lane, Chun-Ying Wu, Graduate Institute of Clinical Medical Science, China Medical University, Taichung 407, Taiwan.
authors.forename: Hsien-Yuan
authors.initials: HY
authors.lastname: Lane
authors.affiliation: Teng-Yu Lee, Hsien-Yuan Lane, Chun-Ying Wu, Graduate Institute of Clinical Medical Science, China Medical University, Taichung 407, Taiwan.
authors.forename: Jaw-Town
authors.initials: JT
authors.lastname: Lin
authors.affiliation: Teng-Yu Lee, Hsien-Yuan Lane, Chun-Ying Wu, Graduate Institute of Clinical Medical Science, China Medical University, Taichung 407, Taiwan.
authors.forename: Chun-Ying
authors.initials: CY
authors.lastname: Wu
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood*; D016009:Chi-Square Distribution; D015536:Down-Regulation; D005260:Female; D005492:Folic Acid / Q000097:blood*; D005743:Gastrectomy; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D016017:Odds Ratio; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000097:blood* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D013624:Taiwan; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D005492:Folic Acid
keywords: Folate; Folic acid; Invasion; Metastasis; Plasma