Dataset Information

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]

PMID: 23737080

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Project description:PURPOSE: Several dietary factors have been associated with glaucoma. Among them, dietary antioxidant intake (i.e., vitamin C and vitamin A) in association with glaucoma has been analyzed, but with mixed results. Genetic factors may play a role in modulating the effect of dietary antioxidant intake on glaucoma; however, nutrigenetic studies in this field are scarce. Our aim was to study the association between selected polymorphisms in key proteins related to vitamin C and vitamin A concentrations and primary open-angle glaucoma (POAG). METHODS: We performed a case-control study matched for age, sex, and bodyweight. We recruited 300 subjects (150 POAG cases and 150 controls) from a Mediterranean population and determined the plasma concentrations of vitamin C and vitamin A for each subject. We selected the following single-nucleotide polymorphisms (SNPs) in genes related to vitamin A and vitamin C concentrations: rs176990 and rs190910 in the retinol-binding protein 1 (RBP1) gene; and rs10063949 and rs1279683 in the Na?-dependent L-ascorbic acid transporters 1 and 2, respectively (encoded by the SLC23A1 and SLC23A2 genes). RESULTS: We found a statistically significant association between the rs1279386 (A>G) SNP in SLC23A2 and POAG risk. In the crude analysis, homozygous subjects for the G allele (GG subjects) had higher risk of POAG than other genotypes (OR: 1.67; 95% CI: 1.03-2.71). This association remained statistically significant (p=0.010) after multivariate adjustment for potential confounders. We also found that POAG patients had lower plasma vitamin C concentrations than control subjects (9.9±1.7 µg/ml versus 11.7±1.8 µg/ml, p<0.001). Moreover, we consistently detected a significant association between the rs1279386 SNP in SLC23A2 and plasma vitamin C concentrations: GG subjects had significantly lower plasma vitamin C concentrations than the other genotypes (9.0±1.4 µg/ml versus 10.5±1.6 µg/ml, p<0.001 in POAG cases and 10.9±1.6 µg/ml versus 12.1±1.8 µg/ml, p<0.001 in controls). The rs10063949 SNP in SLC23A1 was not associated with either plasma vitamin C concentrations or POAG risk. Similarly, SNPs in RBP1 were not associated with vitamin A concentrations or POAG risk. CONCLUSIONS: The rs1279683 SNP in SLC23A2 was significantly associated with lower plasma concentrations of vitamin C and with higher risk of POAG in GG subjects.

Dataset Information

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

Publications

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

Similar Datasets

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