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


ABSTRACT: 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.

SUBMITTER: Duell EJ 

PROVIDER: S-EPMC3824828 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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

Duell Eric J EJ   Lujan-Barroso Leila L   Llivina Claudia C   Muñoz Xavier X   Jenab Mazda M   Boutron-Ruault Marie-Christine MC   Clavel-Chapelon Françoise F   Racine Antoine A   Boeing Heiner H   Buijsse Brian B   Canzian Federico F   Johnson Theron T   Dalgård Christine C   Overvad Kim K   Tjønneland Anne A   Olsen Anja A   Sánchez Soledad C SC   Sánchez-Cantalejo Emilio E   Huerta José-María JM   Ardanaz Eva E   Dorronsoro Miren M   Khaw Kay-Tee KT   Travis Ruth C RC   Trichopoulou Antonia A   Trichopoulos Dimitrios D   Rafnsson Snorri S   Palli Domenico D   Sacerdote Carlotta C   Tumino Rosario R   Panico Salvatore S   Grioni Sara S   Bueno-de-Mesquita H Bas HB   Ros Martine M MM   Numans Mattijs E ME   Peeters Petra H PH   Johansen Dorthe D   Lindkvist Björn B   Johansson Mattias M   Johansson Ingegerd I   Skeie Guri G   Weiderpass Elisabete E   Duarte-Salles Talita T   Stenling Roger R   Riboli Elio E   Sala Núria N   González Carlos A CA  

Genes & nutrition 20130605 6


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 eva  ...[more]

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