Circulating 25-hydroxyvitamin D and risk of esophageal and gastric cancer: Cohort Consortium Vitamin D Pooling Project of Rarer Cancers

Abstract

Upper gastrointestinal (GI) cancers of the stomach and esophagus have high incidence and mortality worldwide, but they are uncommon in Western countries. Little information exists on the association between vitamin D and risk of upper GI cancers. This study examined the association between circulating 25-hydroxyvitamin D (25(OH)D) and upper GI cancer risk in the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers. Concentrations of 25(OH)D were measured from 1,065 upper GI cancer cases and 1,066 age-, sex-, race-, and season-of blood draw-matched controls from 8 prospective cohort studies. In multivariate-adjusted models, circulating 25(OH)D concentration was not significantly associated with upper GI cancer risk. Subgroup analysis by race showed that among Asians, but not Caucasians, lower concentrations of 25(OH)D (<25 nmol/L) were associated with a statistically significant decreased risk of upper GI cancer (reference: 50-<75 nmol/L) (odds ratio = 0.53, 95% confidence interval: 0.31, 0.91; P trend = 0.003). Never smokers with concentrations of <25 nmol/L showed a lower risk of upper GI cancers (odds ratio = 0.55, 95% confidence interval: 0.31, 0.96). Subgroup analyses by alcohol consumption produced opposing trends. Results do not support the hypothesis that interventions aimed at increasing vitamin D status would lead to a lower risk of these highly fatal cancers.

Figure 1.

Forest plots for the meta-analysis of the association between circulating 25-hydroxyvitamin D (25(OH)D) and the risk of esophageal and gastric cancer within the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers. Risk estimates, by cohort, for subjects with circulating 25(OH)D concentrations of A) <25 nmol/L and B) ≥75 nmol/L compared with the referent group (50–<75 nmol/L). Odds ratios (ORs) and 95% confidence intervals (CIs) were derived from conditional logistic regression models. The boxes show the odds ratios, the bars show the 95% confidence intervals, and the size of each box is inversely proportional to the variance of the log odds ratio estimate in each cohort. The overall estimates (diamonds) were derived from a meta-analysis using random-effects modeling. No estimates are given for the NYU-WHS because of small numbers in the exposed group. For the <25 nmol/L comparison, I² was 39%; for the ≥75 nmol/L comparison, I² was 9%. ATBC, Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study; CPS-II, Cancer Prevention Study II Nutrition Cohort; GI, gastrointestinal; MEC, Multiethnic Cohort Study; NYU-WHS, New York University Women's Health Study; PLCO, Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial; SMHS/SWHS, Shanghai Men's Health Study/Shanghai Women's Health Study.