Plasma and dietary vitamin C levels and risk of gastric cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC-EURGAST)

Abstract

Vitamin C is an antioxidant and inhibitor of carcinogenic N-nitroso compound production in the stomach. Higher dietary vitamin C consumption is associated with decreased risk of gastric cancer (GC) in numerous case-control studies, but data from prospective studies are limited, particularly so for blood measures of vitamin C. The objective of this study was to determine the association of plasma and dietary vitamin C levels with the risk of GC in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), a large cohort involving 10 European countries. Using a fluorometric method, vitamin C was measured in pre-diagnostic plasma from 215 GC cases (matched controls = 416). Conditional logistic regression models adjusted by body mass index, total energy intake, smoking status/duration/intensity and Helicobacter pylori infection status were used to estimate relative cancer risks. No association with GC risk was observed for dietary vitamin C, whereas an inverse GC risk was observed in the highest versus lowest quartile of plasma vitamin C [odds ratio (OR) = 0.55, 95% confidence interval (CI) = 0.31-0.97, P(trend) = 0.043], which was maintained after exclusion of cases with <or=2 years follow-up (OR = 0.40, 95% CI = 0.19-0.83, P(trend) = 0.064). The inverse association was more pronounced in subjects consuming higher levels of red and processed meats, a factor that may increase endogenous N-nitroso compound production. The effect of plasma vitamin C was not different by GC anatomical subsite (cardia/non-cardia) or histological subtype (diffuse/intestinal), and there was no significant interaction of effect with H.pylori. The results of this study show, in a prospective setting, an inverse association of GC risk with high levels of plasma vitamin C and suggest an interaction with the intake of red and processed meats, whose consumption may elevate endogenous N-nitroso compound production.

Body Mass and Physical Activity and Risk of Gastric Cancer in a Population-Based Cohort Study in Norway

“…Moreover, no detailed information on nutritional factors was available (e.g., intake of antioxidative vitamins, which may have a protective effect against gastric cancer; refs. [24][25][26]. It is plausible that such dietary factors could be associated with weight and level of physical activity, and obese persons tend to have lower blood levels of antioxidants (27,28).…”

Diet and the risk of gastric cancer: review of epidemiological evidence

“…A nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC) compared the levels of dietary and prediagnostic plasma vitamin C between 215 gastric cancer cases and 416 matched controls [46]. No association with gastric cancer risk was observed for dietary vitamin C, whereas an inverse association was seen in the highest versus lowest quartile of plasma vitamin C (OR = 0.55, 95% CI = 0.31-0.97; for trend, P = 0.04).…”

Vitamin C transporter gene (SLC23A1 and SLC23A2) polymorphisms, plasma vitamin C levels, and gastric cancer risk in the EPIC cohort

“…The magnitude of the inverse association between plasma vitamin C concentration and GC risk previously reported in EPIC was moderate (highest vs. lowest quartile, OR 0.55, 95 % CI 0.31-0.97) representing a 45 % lower risk (Jenab et al 2006b). In the previous analysis which included fewer GC cases (n = 215), questionnaire-based vitamin C intake from foods was not associated with GC risk (Jenab et al 2006b); however, with additional GC cases in the present analysis (n = 365), higher intakes of vitamin C from foods were statistically significantly associated with reduced GC risk. In contrast, questionnaire-based vitamin C intake was not a strong predictor of plasma vitamin C concentration in our study, and none of the SNP markers we tested improved this prediction.…”

“…Vitamin C levels (lmol/L) were previously determined in thawed plasma samples using a fluorometric method described in detail in our previous study of vitamin C levels and GC risk (Vuilleumier and Keck 1989;Jenab et al 2006b). The effect of long-term cryopreservation on the stability of plasma vitamin C in the EPIC cohort also has been previously described, and in brief, while samples with higher baseline concentrations tended to lose more vitamin C than samples with lower concentrations, the methods and assays for plasma vitamin C concentration were determined to be reliable without the addition of stabilizing agents (Jenab et al 2005).…”