Previous studies have found associations between one-
carbon metabolism nutrients and risk of several
cancers, but little is known regarding upper gastrointestinal tract (UGI)
cancer. We analyzed prediagnostic serum concentrations of several one-
carbon metabolism nutrients (
vitamin B12,
folate,
vitamin B6,
riboflavin and
homocysteine) in a nested case-control study within the
Alpha-Tocopherol,
Beta-Carotene Cancer Prevention (ATBC) Study of male smokers, which was undertaken in Finland between 1985 and 1988. We conducted a nested case-control study including 127 noncardia gastric
adenocarcinoma (
NCGA), 41 esophagogastric junctional
adenocarcinoma and 60
esophageal squamous cell carcinoma incident cases identified within ATBC. Controls were matched to cases on age, date of serum collection and follow-up time. One-
carbon nutrient concentrations were measured in fasting serum samples collected at baseline (up to 17 years prior to
cancer diagnosis). Odds ratios and 95% confidence intervals (CI) were calculated using conditional logistic regression. Lower prediagnostic
vitamin B12 concentrations at baseline were associated with a 5.8-fold increased risk of
NCGA (95% CI = 2.7-12.6 for lowest compared to highest quartile, p-trend <0.001). This association remained in participants who developed
cancer more than 10 years after blood collection, and after restricting the analysis to participants with clinically normal serum
vitamin B12 (>300 pmol/L). In contrast,
pepsinogen I, a known serologic marker of gastric
atrophy, was not associated with
NCGA in this population. As
vitamin B12 absorption requires intact gastric mucosa to produce
acid and
intrinsic factor, our findings suggest
vitamin B12 as a possible serologic marker for the
atrophic gastritis that precedes
NCGA, one more strongly associated with subsequent
NCGA than
pepsinogen.