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

E. J. Duell, L. Lujan-Barroso, C. Llivina, X. Munoz, M. Jenab, M. C. Boutron-Ruault, F. Clavel-Chapelon, A. Racine, H. Boeing, B. Buijsse, F. Canzian, T. Johnson, Christine Dalgård, K. Overvad, A. Tjonneland, A. Olsen, S. C. Sanchez, E. Sanchez-Cantalejo, J. M. Huerta, E. Ardanaz & 26 andre M. Dorronsoro, K. T. Khaw, R. C. Travis, A. Trichopoulou, D. Trichopoulos, S. Rafnsson, D. Palli, C. Sacerdote, R. Tumino, S. Panico, S. Grioni, H. B. Bueno-de-Mesquita, M. M. Ros, M. E. Numans, P. H. Peeters, D. Johansen, B. Lindkvist, M. Johansson, I. Johansson, G. Skeie, E. Weiderpass, T. Duarte-Salles, R. Stenling, E. Riboli, N. Sala, C. A. Gonzalez

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

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.
OriginalsprogEngelsk
TidsskriftGenes & Nutrition
Vol/bind8
Udgave nummer6
Sider (fra-til)549-560
ISSN1555-8932
DOI
StatusUdgivet - 2013

Fingeraftryk

Sodium-Coupled Vitamin C Transporters
Haplotypes
Single Nucleotide Polymorphism
Linear Models
Logistic Models
Intestinal Neoplasms
Nitrosamines
Citrus
Mucous Membrane

Citer dette

Duell, E. J., Lujan-Barroso, L., Llivina, C., Munoz, X., Jenab, M., Boutron-Ruault, M. C., ... Gonzalez, C. A. (2013). Vitamin C transporter gene (SLC23A1 and SLC23A2) polymorphisms, plasma vitamin C levels, and gastric cancer risk in the EPIC cohort. Genes & Nutrition, 8(6), 549-560. https://doi.org/10.1007/s12263-013-0346-6
Duell, E. J. ; Lujan-Barroso, L. ; Llivina, C. ; Munoz, X. ; Jenab, M. ; Boutron-Ruault, M. C. ; Clavel-Chapelon, F. ; Racine, A. ; Boeing, H. ; Buijsse, B. ; Canzian, F. ; Johnson, T. ; Dalgård, Christine ; Overvad, K. ; Tjonneland, A. ; Olsen, A. ; Sanchez, S. C. ; Sanchez-Cantalejo, E. ; Huerta, J. M. ; Ardanaz, E. ; Dorronsoro, M. ; Khaw, K. T. ; Travis, R. C. ; Trichopoulou, A. ; Trichopoulos, D. ; Rafnsson, S. ; Palli, D. ; Sacerdote, C. ; Tumino, R. ; Panico, S. ; Grioni, S. ; Bueno-de-Mesquita, H. B. ; Ros, M. M. ; Numans, M. E. ; Peeters, P. H. ; Johansen, D. ; Lindkvist, B. ; Johansson, M. ; Johansson, I. ; Skeie, G. ; Weiderpass, E. ; Duarte-Salles, T. ; Stenling, R. ; Riboli, E. ; Sala, N. ; Gonzalez, C. A. / Vitamin C transporter gene (SLC23A1 and SLC23A2) polymorphisms, plasma vitamin C levels, and gastric cancer risk in the EPIC cohort. I: Genes & Nutrition. 2013 ; Bind 8, Nr. 6. s. 549-560.
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title = "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.",
keywords = "Gastric cancer Vitamin C Antioxidants Genetic susceptibility SLC23A1 SLC23A2 HELICOBACTER-PYLORI INFECTION ASCORBIC-ACID TRANSPORTERS VEGETABLE INTAKE NUTRITION EURGAST ADENOCARCINOMAS FRUIT",
author = "Duell, {E. J.} and L. Lujan-Barroso and C. Llivina and X. Munoz and M. Jenab and Boutron-Ruault, {M. C.} and F. Clavel-Chapelon and A. Racine and H. Boeing and B. Buijsse and F. Canzian and T. Johnson and Christine Dalg{\aa}rd and K. Overvad and A. Tjonneland and A. Olsen and Sanchez, {S. C.} and E. Sanchez-Cantalejo and Huerta, {J. M.} and E. Ardanaz and M. Dorronsoro and Khaw, {K. T.} and Travis, {R. C.} and A. Trichopoulou and D. Trichopoulos and S. Rafnsson and D. Palli and C. Sacerdote and R. Tumino and S. Panico and S. Grioni and Bueno-de-Mesquita, {H. B.} and Ros, {M. M.} and Numans, {M. E.} and Peeters, {P. H.} and D. Johansen and B. Lindkvist and M. Johansson and I. Johansson and G. Skeie and E. Weiderpass and T. Duarte-Salles and R. Stenling and E. Riboli and N. Sala and Gonzalez, {C. A.}",
year = "2013",
doi = "10.1007/s12263-013-0346-6",
language = "English",
volume = "8",
pages = "549--560",
journal = "Genes & Nutrition",
issn = "1555-8932",
publisher = "BioMed Central",
number = "6",

}

Duell, EJ, Lujan-Barroso, L, Llivina, C, Munoz, X, Jenab, M, Boutron-Ruault, MC, Clavel-Chapelon, F, Racine, A, Boeing, H, Buijsse, B, Canzian, F, Johnson, T, Dalgård, C, Overvad, K, Tjonneland, A, Olsen, A, Sanchez, SC, Sanchez-Cantalejo, E, Huerta, JM, Ardanaz, E, Dorronsoro, M, Khaw, KT, Travis, RC, Trichopoulou, A, Trichopoulos, D, Rafnsson, S, Palli, D, Sacerdote, C, Tumino, R, Panico, S, Grioni, S, Bueno-de-Mesquita, HB, Ros, MM, Numans, ME, Peeters, PH, Johansen, D, Lindkvist, B, Johansson, M, Johansson, I, Skeie, G, Weiderpass, E, Duarte-Salles, T, Stenling, R, Riboli, E, Sala, N & Gonzalez, CA 2013, 'Vitamin C transporter gene (SLC23A1 and SLC23A2) polymorphisms, plasma vitamin C levels, and gastric cancer risk in the EPIC cohort', Genes & Nutrition, bind 8, nr. 6, s. 549-560. https://doi.org/10.1007/s12263-013-0346-6

Vitamin C transporter gene (SLC23A1 and SLC23A2) polymorphisms, plasma vitamin C levels, and gastric cancer risk in the EPIC cohort. / Duell, E. J.; Lujan-Barroso, L.; Llivina, C.; Munoz, X.; Jenab, M.; Boutron-Ruault, M. C.; Clavel-Chapelon, F.; Racine, A.; Boeing, H.; Buijsse, B.; Canzian, F.; Johnson, T.; Dalgård, Christine; Overvad, K.; Tjonneland, A.; Olsen, A.; Sanchez, S. C.; Sanchez-Cantalejo, E.; Huerta, J. M.; Ardanaz, E.; Dorronsoro, M.; Khaw, K. T.; Travis, R. C.; Trichopoulou, A.; Trichopoulos, D.; Rafnsson, S.; Palli, D.; Sacerdote, C.; Tumino, R.; Panico, S.; Grioni, S.; Bueno-de-Mesquita, H. B.; Ros, M. M.; Numans, M. E.; Peeters, P. H.; Johansen, D.; Lindkvist, B.; Johansson, M.; Johansson, I.; Skeie, G.; Weiderpass, E.; Duarte-Salles, T.; Stenling, R.; Riboli, E.; Sala, N.; Gonzalez, C. A.

I: Genes & Nutrition, Bind 8, Nr. 6, 2013, s. 549-560.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Vitamin C transporter gene (SLC23A1 and SLC23A2) polymorphisms, plasma vitamin C levels, and gastric cancer risk in the EPIC cohort

AU - Duell, E. J.

AU - Lujan-Barroso, L.

AU - Llivina, C.

AU - Munoz, X.

AU - Jenab, M.

AU - Boutron-Ruault, M. C.

AU - Clavel-Chapelon, F.

AU - Racine, A.

AU - Boeing, H.

AU - Buijsse, B.

AU - Canzian, F.

AU - Johnson, T.

AU - Dalgård, Christine

AU - Overvad, K.

AU - Tjonneland, A.

AU - Olsen, A.

AU - Sanchez, S. C.

AU - Sanchez-Cantalejo, E.

AU - Huerta, J. M.

AU - Ardanaz, E.

AU - Dorronsoro, M.

AU - Khaw, K. T.

AU - Travis, R. C.

AU - Trichopoulou, A.

AU - Trichopoulos, D.

AU - Rafnsson, S.

AU - Palli, D.

AU - Sacerdote, C.

AU - Tumino, R.

AU - Panico, S.

AU - Grioni, S.

AU - Bueno-de-Mesquita, H. B.

AU - Ros, M. M.

AU - Numans, M. E.

AU - Peeters, P. H.

AU - Johansen, D.

AU - Lindkvist, B.

AU - Johansson, M.

AU - Johansson, I.

AU - Skeie, G.

AU - Weiderpass, E.

AU - Duarte-Salles, T.

AU - Stenling, R.

AU - Riboli, E.

AU - Sala, N.

AU - Gonzalez, C. A.

PY - 2013

Y1 - 2013

N2 - 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.

AB - 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.

KW - Gastric cancer Vitamin C Antioxidants Genetic susceptibility SLC23A1 SLC23A2 HELICOBACTER-PYLORI INFECTION ASCORBIC-ACID TRANSPORTERS VEGETABLE INTAKE NUTRITION EURGAST ADENOCARCINOMAS FRUIT

U2 - 10.1007/s12263-013-0346-6

DO - 10.1007/s12263-013-0346-6

M3 - Journal article

VL - 8

SP - 549

EP - 560

JO - Genes & Nutrition

JF - Genes & Nutrition

SN - 1555-8932

IS - 6

ER -