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

Eric J. Duell, Leila Lujan-Barroso, Claudia Llivina, Xavier Muñoz, Mazda Jenab, Marie Christine Boutron-Ruault, Françoise Clavel-Chapelon, Antoine Racine, Heiner Boeing, Brian Buijsse, Federico Canzian, Theron Johnson, Christine Dalgård, Kim Overvad, Anne Tjønneland, Anja Olsen, Soledad C. Sánchez, Emilio Sánchez-Cantalejo, José María Huerta, Eva ArdanazMiren Dorronsoro, Kay Tee Khaw, Ruth C. Travis, Antonia Trichopoulou, Dimitrios Trichopoulos, Snorri Rafnsson, Domenico Palli, Carlotta Sacerdote, Rosario Tumino, Salvatore Panico, Sara Grioni, H. Bas Bueno-De-Mesquita, Martine M. Ros, Mattijs E. Numans, Petra H. Peeters, Dorthe Johansen, Björn Lindkvist, Mattias Johansson, Ingegerd Johansson, Guri Skeie, Elisabete Weiderpass, Talita Duarte-Salles, Roger Stenling, Elio Riboli, Núria Sala, Carlos A. González

Research output: Contribution to journalArticlepeer-review


Vitamin C is known to protect mucosal tissues from oxidative stress and inhibit nitrosamine formation in the stomach. High consumption of fruits, particularly citrus, and higher circulating vitamin C concentrations may be inversely associated with gastric cancer (GC) risk. We investigated 20 polymorphisms in vitamin C transporter genes SCL23A1 and SCL23A2 and GC risk in 365 cases and 1,284 controls nested within the European Prospective Investigation into Cancer and Nutrition cohort. We also evaluated the association between these polymorphisms and baseline plasma vitamin C levels in a subset of participants. Four SNPs were predictors of plasma vitamin C levels (SLC23A1 rs11950646 and rs33972313; SLC23A2 rs6053005 and rs6133175) in multivariable linear regression models. One SNP (SLC23A2 rs6116569) was associated with GC risk, in particular non-cardia GC (OR = 1.63, 95 % CI = 1.11-2.39, based on 178 non-cardia cases), but this association was attenuated when plasma vitamin C was included in the logistic regression model. Haplotype analysis of SLC23A1 yielded no associations with GC. In SLC23A2, one haplotype was associated with both overall and non-cardia GC, another haplotype was associated with GC overall, and a third was associated with intestinal-type GC. Common variants in SLC23A1 and SLC23A2 may influence plasma vitamin C concentration independent of dietary intake, and variation in SLC23A2 may influence GC risk. Additional prospective studies in large populations and consortia are recommended. Investigation of variation in vitamin C transporter genes may shed light on the preventative properties of vitamin C in gastric carcinogenesis.

Original languageEnglish
Pages (from-to)549-560
Number of pages12
JournalGenes and Nutrition
Issue number6
Publication statusPublished - Nov 2013


  • Antioxidants
  • Gastric cancer
  • Genetic susceptibility
  • SLC23A1
  • SLC23A2
  • Vitamin C

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Genetics


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