Intakes of folate, methionine, vitamin B6, and vitamin B12 with risk of esophageal and gastric cancer in a large cohort study

Abstract

Background: Nutrients in the one-carbon metabolism pathway may be involved in carcinogenesis. Few cohort studies have investigated the intakes of folate and related nutrients in relation to gastric and esophageal cancer.

Methods: We prospectively examined the association between self-reported intakes of folate, methionine, vitamin B6, and vitamin B12 and gastric and esophageal cancer in 492,293 men and women.

Results: We observed an elevated risk of esophageal squamous cell carcinoma with low intake of folate (relative risk (95% confidence interval): Q1 vs Q3, 1.91 (1.17, 3.10)), but no association with high intake. Folate intake was not associated with esophageal adenocarcinoma, gastric cardia adenocarcinoma, or non-cardia gastric adenocarcinoma. The intakes of methionine, vitamin B6, and vitamin B12 were not associated with esophageal and gastric cancer.

Conclusion: Low intake of folate was associated with increased risk of esophageal squamous cell carcinoma.

Figure 1

The multivariate association of total folate intake with esophageal squamous cell carcinoma and esophageal adenocarcinoma. Multivariate RRs and 95% CIs of risk of (A) esophageal squamous cell carcinoma and (B) esophageal adenocarcinoma for categories of total intake (dietary and supplemental intake combined) of folate in the NIH-AARP study. Squares represent the HRs corresponding to each intake category. Vertical lines represent the 95% CIs. Models were adjusted for age at baseline (continuous); sex (male and female); race/ethnicity (non-Hispanic white, non-Hispanic, black, and others); education (less than high school, high school graduate, some college and college graduate/postgraduate); marital status (married, not married), health status (excellent, very good, good, fair, and poor); BMI (<18.5, 18.5–<25, 25–<30, 30–<35, ⩾35 kg m⁻²); smoking status (never, former, and current); smoking dose (0, 1–10, 11–20, 21–30, 31–40, 41–50, 51–60, and >60 cigarettes per day); time since quitting (never quit, ⩾10, 5–9, 1–4, <1 years); vigorous physical activity (never/rarely; ⩽3 times per month; 1–2, 3–4, and ⩾5 times per week); alcohol (0, <5, 5–<15, 15–<30, and ⩾30 g per day); multivitamin use (nonuse, less than daily use, and daily use); family history of any cancer (yes or no), and total caloric intake (continuous). The numbers of cases were 19, 39, 36, 42, and 39 ESCC and 62, 121, 136, 132, and 68 EAC for categories of <300, 300–<400, 400–<600, 500–<800, and 800+ mcg per day, respectively.