Serum Vitamin B12 And Development Of Non-Cardia Gastric Cancer: A Prospective Study

Background: The pathogenesis of non-cardia gastric adenocarcinoma (NCGA) begins with Helicobacter pylori (Hp) infection, which induces atrophic gastritis, a pre-neoplastic state characterized by gland loss and achlorhydria. In parallel, vitamin B12 absorption requires intact gastric mucosa which can produce acid and intrinsic factor. Several previous studies have suggested that Hp infection, the primary risk factor for NCGA, impairs vitamin B12 absorption. Other studies have shown that previous diagnosis of pernicious anemia, the most common form of vitamin B12 deficiency and autoimmune atrophic gastritis, predicts later NCGA. We hypothesized that decreased serum vitamin B12 would predict subsequent incidence of NCGA in a dose-dependent fashion. Methods: To examine the relationship between serum vitamin B12 and risk of NCGA, we conducted a nested case-control study within the prospective Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study of male Finnish smokers aged 50-69 at baseline (1985-1988). Vitamin B12 concentrations were measured in serum samples that were collected at study enrollment. Subjects were followed for 17 years for cancer development (mean time to NCGA diagnosis = 7.5 years). 177 NCGA cases were matched 1:1 on age and date of serum collection with cancer-free controls. We calculated odds ratios (OR) and 95% confidence intervals (CI) by conditional logistic regression, controlling for Hp infection, smoking, fruit and vegetable intake, and other potential confounders. Results: Baseline mean pre-diagnostic serum vitamin B12 concentrations were 16% lower in subjects who subsequently developed NCGA (Cases: 435 pg/mL, SE = 129; Controls: 516 pg/mL, SE = 207; p = 0.0001; serum vitamin B12 levels u003e200 pg/mL are clinically normal.) Lower serum vitamin B12 at baseline was associated with subsequent incidence of NCGA during follow-up (OR = 7.24; 95% CI = 2.12 to 24.73 for lowest quartile compared to highest, p-trend = 0.002). This association remained after restricting the analysis to subjects who developed cancer more than 10 years after baseline serum vitamin B12 measurements. Conclusion: Lower serum vitamin B12 concentrations were associated with an increased risk of NCGA even among subjects who were diagnosed more than 10 years after their enrollment in the study. Our findings suggest a possible role for serum vitamin B12 as a biomarker for the atrophic gastritis that precedes NCGA. Citation Format: Eugenia Miranti, Rachael Stolzenberg-Solomon, Stephanie Weinstein, Jacob Selhub, Satu Mannisto, Philip R. Taylor, Neal D. Freedman, Demetrius Albanes, Christian Abnet, Gwen Murphy. Serum vitamin B12 and development of non-cardia gastric cancer: a prospective study. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4301.