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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.; Lujan-Barroso, Leila; Llivina, Claudia; Munoz, Xavier; Jenab, Mazda; Boutron-Ruault, Marie-Christine; Clavel-Chapelon, Francoise; Racine, Antoine; Boeing, Heiner and Buijsse, Brian, et al. (2013) In Genes & Nutrition 8(6). p.549-560
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... (More)
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. (Less)
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keywords
Gastric cancer, Vitamin C, Antioxidants, Genetic susceptibility, SLC23A1, SLC23A2
in
Genes & Nutrition
volume
8
issue
6
pages
549 - 560
publisher
New Century Health Publishers
external identifiers
  • wos:000326103200003
  • scopus:84887237682
ISSN
1555-8932
DOI
10.1007/s12263-013-0346-6
language
English
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yes
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0df9ffa2-5c70-43b0-aaac-90685e58e091 (old id 4204463)
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2014-01-03 10:42:13
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2019-05-14 01:33:52
@article{0df9ffa2-5c70-43b0-aaac-90685e58e091,
  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.},
  author       = {Duell, Eric J. and Lujan-Barroso, Leila and Llivina, Claudia and Munoz, Xavier and Jenab, Mazda and Boutron-Ruault, Marie-Christine and Clavel-Chapelon, Francoise and Racine, Antoine and Boeing, Heiner and Buijsse, Brian and Canzian, Federico and Johnson, Theron and Dalgard, Christine and Overvad, Kim and Tjonneland, Anne and Olsen, Anja and Sanchez, Soledad C. and Sanchez-Cantalejo, Emilio and Huerta, Jose-Maria and Ardanaz, Eva and Dorronsoro, Miren and Khaw, Kay-Tee and Travis, Ruth C. and Trichopoulou, Antonia and Trichopoulos, Dimitrios and Rafnsson, Snorri and Palli, Domenico and Sacerdote, Carlotta and Tumino, Rosario and Panico, Salvatore and Grioni, Sara and Bueno-de-Mesquita, H. Bas and Ros, Martine M. and Numans, Mattijs E. and Peeters, Petra H. and Johansen, Dorthe and Lindkvist, Bjorn and Johansson, Mattias and Johansson, Ingegerd and Skeie, Guri and Weiderpass, Elisabete and Duarte-Salles, Talita and Stenling, Roger and Riboli, Elio and Sala, Nuria and Gonzalez, Carlos A.},
  issn         = {1555-8932},
  keyword      = {Gastric cancer,Vitamin C,Antioxidants,Genetic susceptibility,SLC23A1,SLC23A2},
  language     = {eng},
  number       = {6},
  pages        = {549--560},
  publisher    = {New Century Health Publishers},
  series       = {Genes & Nutrition},
  title        = {Vitamin C transporter gene (SLC23A1 and SLC23A2) polymorphisms, plasma vitamin C levels, and gastric cancer risk in the EPIC cohort},
  url          = {http://dx.doi.org/10.1007/s12263-013-0346-6},
  volume       = {8},
  year         = {2013},
}