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

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 polymor...

Full description

Bibliographic Details
Main Authors: Duell, E, Lujan-Barroso, L, Llivina, C, Muñoz, X, Jenab, M, Boutron-Ruault, M, Clavel-Chapelon, F, Racine, A, Boeing, H, Buijsse, B, Canzian, F, Johnson, T, Dalgård, C, Overvad, K, Tjønneland, A, Olsen, A, Sánchez, S, Sánchez-Cantalejo, E, Huerta, J, Ardanaz, E, Dorronsoro, M, Khaw, K, Travis, R, Trichopoulou, A, Trichopoulos, D
Format: Journal article
Language:English
Published: 2013
_version_ 1826261311795757056
author Duell, E
Lujan-Barroso, L
Llivina, C
Muñoz, X
Jenab, M
Boutron-Ruault, M
Clavel-Chapelon, F
Racine, A
Boeing, H
Buijsse, B
Canzian, F
Johnson, T
Dalgård, C
Overvad, K
Tjønneland, A
Olsen, A
Sánchez, S
Sánchez-Cantalejo, E
Huerta, J
Ardanaz, E
Dorronsoro, M
Khaw, K
Travis, R
Trichopoulou, A
Trichopoulos, D
author_facet Duell, E
Lujan-Barroso, L
Llivina, C
Muñoz, X
Jenab, M
Boutron-Ruault, M
Clavel-Chapelon, F
Racine, A
Boeing, H
Buijsse, B
Canzian, F
Johnson, T
Dalgård, C
Overvad, K
Tjønneland, A
Olsen, A
Sánchez, S
Sánchez-Cantalejo, E
Huerta, J
Ardanaz, E
Dorronsoro, M
Khaw, K
Travis, R
Trichopoulou, A
Trichopoulos, D
author_sort Duell, E
collection OXFORD
description 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. © 2013 Springer-Verlag Berlin Heidelberg.
first_indexed 2024-03-06T19:19:24Z
format Journal article
id oxford-uuid:198d0dd9-8c6b-4cd1-9651-36e50bdc5668
institution University of Oxford
language English
last_indexed 2024-03-06T19:19:24Z
publishDate 2013
record_format dspace
spelling oxford-uuid:198d0dd9-8c6b-4cd1-9651-36e50bdc56682022-03-26T10:49:36ZVitamin C transporter gene (SLC23A1 and SLC23A2) polymorphisms, plasma vitamin C levels, and gastric cancer risk in the EPIC cohortJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:198d0dd9-8c6b-4cd1-9651-36e50bdc5668EnglishSymplectic Elements at Oxford2013Duell, ELujan-Barroso, LLlivina, CMuñoz, XJenab, MBoutron-Ruault, MClavel-Chapelon, FRacine, ABoeing, HBuijsse, BCanzian, FJohnson, TDalgård, COvervad, KTjønneland, AOlsen, ASánchez, SSánchez-Cantalejo, EHuerta, JArdanaz, EDorronsoro, MKhaw, KTravis, RTrichopoulou, ATrichopoulos, DVitamin 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. © 2013 Springer-Verlag Berlin Heidelberg.
spellingShingle Duell, E
Lujan-Barroso, L
Llivina, C
Muñoz, X
Jenab, M
Boutron-Ruault, M
Clavel-Chapelon, F
Racine, A
Boeing, H
Buijsse, B
Canzian, F
Johnson, T
Dalgård, C
Overvad, K
Tjønneland, A
Olsen, A
Sánchez, S
Sánchez-Cantalejo, E
Huerta, J
Ardanaz, E
Dorronsoro, M
Khaw, K
Travis, R
Trichopoulou, A
Trichopoulos, D
Vitamin C transporter gene (SLC23A1 and SLC23A2) polymorphisms, plasma vitamin C levels, and gastric cancer risk in the EPIC cohort
title Vitamin C transporter gene (SLC23A1 and SLC23A2) polymorphisms, plasma vitamin C levels, and gastric cancer risk in the EPIC cohort
title_full Vitamin C transporter gene (SLC23A1 and SLC23A2) polymorphisms, plasma vitamin C levels, and gastric cancer risk in the EPIC cohort
title_fullStr Vitamin C transporter gene (SLC23A1 and SLC23A2) polymorphisms, plasma vitamin C levels, and gastric cancer risk in the EPIC cohort
title_full_unstemmed Vitamin C transporter gene (SLC23A1 and SLC23A2) polymorphisms, plasma vitamin C levels, and gastric cancer risk in the EPIC cohort
title_short Vitamin C transporter gene (SLC23A1 and SLC23A2) polymorphisms, plasma vitamin C levels, and gastric cancer risk in the EPIC cohort
title_sort vitamin c transporter gene slc23a1 and slc23a2 polymorphisms plasma vitamin c levels and gastric cancer risk in the epic cohort
work_keys_str_mv AT duelle vitaminctransportergeneslc23a1andslc23a2polymorphismsplasmavitaminclevelsandgastriccancerriskintheepiccohort
AT lujanbarrosol vitaminctransportergeneslc23a1andslc23a2polymorphismsplasmavitaminclevelsandgastriccancerriskintheepiccohort
AT llivinac vitaminctransportergeneslc23a1andslc23a2polymorphismsplasmavitaminclevelsandgastriccancerriskintheepiccohort
AT munozx vitaminctransportergeneslc23a1andslc23a2polymorphismsplasmavitaminclevelsandgastriccancerriskintheepiccohort
AT jenabm vitaminctransportergeneslc23a1andslc23a2polymorphismsplasmavitaminclevelsandgastriccancerriskintheepiccohort
AT boutronruaultm vitaminctransportergeneslc23a1andslc23a2polymorphismsplasmavitaminclevelsandgastriccancerriskintheepiccohort
AT clavelchapelonf vitaminctransportergeneslc23a1andslc23a2polymorphismsplasmavitaminclevelsandgastriccancerriskintheepiccohort
AT racinea vitaminctransportergeneslc23a1andslc23a2polymorphismsplasmavitaminclevelsandgastriccancerriskintheepiccohort
AT boeingh vitaminctransportergeneslc23a1andslc23a2polymorphismsplasmavitaminclevelsandgastriccancerriskintheepiccohort
AT buijsseb vitaminctransportergeneslc23a1andslc23a2polymorphismsplasmavitaminclevelsandgastriccancerriskintheepiccohort
AT canzianf vitaminctransportergeneslc23a1andslc23a2polymorphismsplasmavitaminclevelsandgastriccancerriskintheepiccohort
AT johnsont vitaminctransportergeneslc23a1andslc23a2polymorphismsplasmavitaminclevelsandgastriccancerriskintheepiccohort
AT dalgardc vitaminctransportergeneslc23a1andslc23a2polymorphismsplasmavitaminclevelsandgastriccancerriskintheepiccohort
AT overvadk vitaminctransportergeneslc23a1andslc23a2polymorphismsplasmavitaminclevelsandgastriccancerriskintheepiccohort
AT tjønnelanda vitaminctransportergeneslc23a1andslc23a2polymorphismsplasmavitaminclevelsandgastriccancerriskintheepiccohort
AT olsena vitaminctransportergeneslc23a1andslc23a2polymorphismsplasmavitaminclevelsandgastriccancerriskintheepiccohort
AT sanchezs vitaminctransportergeneslc23a1andslc23a2polymorphismsplasmavitaminclevelsandgastriccancerriskintheepiccohort
AT sanchezcantalejoe vitaminctransportergeneslc23a1andslc23a2polymorphismsplasmavitaminclevelsandgastriccancerriskintheepiccohort
AT huertaj vitaminctransportergeneslc23a1andslc23a2polymorphismsplasmavitaminclevelsandgastriccancerriskintheepiccohort
AT ardanaze vitaminctransportergeneslc23a1andslc23a2polymorphismsplasmavitaminclevelsandgastriccancerriskintheepiccohort
AT dorronsorom vitaminctransportergeneslc23a1andslc23a2polymorphismsplasmavitaminclevelsandgastriccancerriskintheepiccohort
AT khawk vitaminctransportergeneslc23a1andslc23a2polymorphismsplasmavitaminclevelsandgastriccancerriskintheepiccohort
AT travisr vitaminctransportergeneslc23a1andslc23a2polymorphismsplasmavitaminclevelsandgastriccancerriskintheepiccohort
AT trichopouloua vitaminctransportergeneslc23a1andslc23a2polymorphismsplasmavitaminclevelsandgastriccancerriskintheepiccohort
AT trichopoulosd vitaminctransportergeneslc23a1andslc23a2polymorphismsplasmavitaminclevelsandgastriccancerriskintheepiccohort