Carcinogenesis Advance Access originally published online on June 14, 2006
Carcinogenesis 2006 27(11):2250-2257; doi:10.1093/carcin/bgl096
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Plasma and dietary vitamin C levels and risk of gastric cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC-EURGAST)
1 Nutrition and Hormones Group, IARC-WHO Lyon, France
2 Imperial College London UK
3 Department of Nutrition, Loma Linda University Loma Linda, CA, USA
4 Institute of Cancer Epidemiology, Danish Cancer Society Copenhagen, Denmark
5 Department of Clinical Epidemiology, Aalborg Hospital, Aarhus University Hospital Aalborg, Denmark
6 INSERM, Institut Gustave Roussy Villejuif, France
7 German Institute of Human Nutrition Potsdam-Rehbücke, Germany
8 Division of Clinical Epidemiology, Deutsches Krebsforschungszentrum Heidelberg, Germany
9 Department of Hygiene and Epidemiology, Medical School, University of Athens Greece
10 Nutritional Epidemiology Unit, National Cancer Institute Milan, Italy
11 Department of Clinical and Experimental Medicine, Federico II University Naples, Italy
12 Molecular and Nutritional Epidemiology Unit, CSPO-Scientific Institute of Tuscany Italy
13 University of Turin and CPO-Piemonte Turin, Italy
14 Cancer Registry, Azienda Ospedaliera ‘Civile M.P. Arezzo’ Ragusa, Italy
15 Julius Centre for Health Sciences and Primary Care, University Medical Center Utrecht, The Netherlands
16 Centre for Nutrition and Health, National Institute for Public Health and the Environment Bilthoven, The Netherlands
17 Institute of Community Medicine, University of Tromso Norway
18 Department of Epidemiology, Catalan Institute of Oncology Barcelona (ICO-IDIBELL), Spain
19 Servicio de Epidemiología, Consejería de Sanidad y Consumo Murcia, Spain
20 Andalusian School of Public Health, Granada Spain
21 Public Health Department of Guipuzkoa San Sebastian, Spain
22 Public Health Institute of Navarra Pamplona, Spain
23 Sección Información Sanitaria, Consejería de Salud y Servicios Sanitarios de Asturias Asturias, Spain
24 Department of Public Health and Clinical Nutrition, Nutrition Research, Umeå University, Umeå, Sweden
25 Department of Medical Biosciences, Pathology, Umeå University Umeå, Sweden
26 Department of Medical Epidemiology, Karolinska Instututet Stockholm, Sweden
27 MRC Dunn Human Nutrition Unit, Welcome Trust/MRC Building Cambridge, UK
28 Clinical Gerontology Unit, University of Cambridge Cambridge, UK
29 Cancer Epidemiology Unit, University of Oxford UK
30 Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP) and Medical Faculty of Porto/H.S. Joao Porto, Portugal
31 Institute of Pathology Potsdam, Germany
32 IRIS Research Center, Chiron-Vaccines Siena, Italy.
*To whom correspondence should be addressed. Tel: +0 472 738082; Fax: +0 472 738361; Email: Jenab{at}iarc.fr
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, Ptrend = 0.043], which was maintained after exclusion of cases with 
2 years follow-up (OR = 0.40, 95% CI = 0.19–0.83, Ptrend = 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.
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