TY - JOUR
T1 - Genetic variation in alcohol dehydrogenase (ADH1A, ADH1B, ADH1C, ADH7) and aldehyde dehydrogenase (ALDH2), alcohol consumption and gastric cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort
AU - Duell, Eric J.
AU - Sala, Nuria
AU - Travier, Noemie
AU - Munoz, Xavier
AU - Christine Boutron-Ruault, Marie
AU - Clavel-Chapelon, Francoise
AU - Barricarte, Aurelio
AU - Arriola, Larraitz
AU - Navarro, Carmen
AU - Sanchez-Cantalejo, Emilio
AU - Ramon Quiros, J.
AU - Krogh, Vittorio
AU - Vineis, Paolo
AU - Mattiello, Amalia
AU - Tumino, Rosario
AU - Khaw, Kay-Tee
AU - Wareham, Nicholas
AU - Allen, Naomi E.
AU - Peeters, Petra H.
AU - Numans, Mattijs E.
AU - Bueno-de-Mesquita, H. B.
AU - van Oijen, M. G. H.
AU - Bamia, Christina
AU - Benetou, Vassiliki
AU - Trichopoulos, Dimitrios
AU - Canzian, Federico
AU - Kaaks, Rudolf
AU - Boeing, Heiner
AU - Bergmann, Manuela M.
AU - Lund, Eiliv
AU - Ehrnström, Roy
AU - Johansen, Dorthe
AU - Hallmans, Goran
AU - Stenling, Roger
AU - Tjonneland, Anne
AU - Overvad, Kim
AU - Ostergaard, Jane Nautrup
AU - Ferrari, Pietro
AU - Fedirko, Veronika
AU - Jenab, Mazda
AU - Nesi, Gabriella
AU - Riboli, Elio
AU - Gonzalez, Carlos A.
PY - 2012
Y1 - 2012
N2 - Studies that have examined the association between alcohol consumption and gastric cancer (GC) risk have been inconsistent. We conducted an investigation of 29 genetic variants in alcohol metabolism loci (alcohol dehydrogenase, ADH1 gene cluster: ADH1A, ADH1B and ADH1C; ADH7 and aldehyde dehydrogenase, ALDH2), alcohol intake and GC risk. We analyzed data from a nested case-control study (364 cases and 1272 controls) within the European Prospective Investigation into Cancer and Nutrition cohort. Single nucleotide polymorphisms (SNPs) were genotyped using a customized array. We observed a statistically significant association between a common 3'-flanking SNP near ADH1A (rs1230025) and GC risk [allelic odds ratio (OR)(A v T) = 1.30, 95% confidence interval (CI) = 1.07-1.59]. Two intronic variants, one in ADH1C (rs283411) and one in ALDH2 (rs16941667), also were associated with GC risk (ORT v C = 0.59; 95% CI = 0.38-0.91 and ORT v C = 1.34; 95% CI = 1.00-1.79, respectively). Individuals carrying variant alleles at both ADH1 (rs1230025) and ALDH2 (rs16941667) were twice as likely to develop GC (ORA+T = 2.0; 95% CI = 1.25-3.20) as those not carrying variant alleles. The association between rs1230025 and GC was modified by alcohol intake (< 5 g/day: ORA = 0.89, 95% CI = 0.57-1.39; >= 5 g/day: ORA = 1.45, 95% CI = 1.08-1.94, P-value = 0.05). The association was also modified by ethanol intake from beer. A known functional SNP in ADH1B (rs1229984) was associated with alcohol intake (P-value = 0.04) but not GC risk. Variants in ADH7 were not associated with alcohol intake or GC risk. In conclusion, genetic variants at ADH1 and ALDH2 loci may influence GC risk, and alcohol intake may further modify the effect of ADH1 rs1230025. Additional population-based studies are needed to confirm our results.
AB - Studies that have examined the association between alcohol consumption and gastric cancer (GC) risk have been inconsistent. We conducted an investigation of 29 genetic variants in alcohol metabolism loci (alcohol dehydrogenase, ADH1 gene cluster: ADH1A, ADH1B and ADH1C; ADH7 and aldehyde dehydrogenase, ALDH2), alcohol intake and GC risk. We analyzed data from a nested case-control study (364 cases and 1272 controls) within the European Prospective Investigation into Cancer and Nutrition cohort. Single nucleotide polymorphisms (SNPs) were genotyped using a customized array. We observed a statistically significant association between a common 3'-flanking SNP near ADH1A (rs1230025) and GC risk [allelic odds ratio (OR)(A v T) = 1.30, 95% confidence interval (CI) = 1.07-1.59]. Two intronic variants, one in ADH1C (rs283411) and one in ALDH2 (rs16941667), also were associated with GC risk (ORT v C = 0.59; 95% CI = 0.38-0.91 and ORT v C = 1.34; 95% CI = 1.00-1.79, respectively). Individuals carrying variant alleles at both ADH1 (rs1230025) and ALDH2 (rs16941667) were twice as likely to develop GC (ORA+T = 2.0; 95% CI = 1.25-3.20) as those not carrying variant alleles. The association between rs1230025 and GC was modified by alcohol intake (< 5 g/day: ORA = 0.89, 95% CI = 0.57-1.39; >= 5 g/day: ORA = 1.45, 95% CI = 1.08-1.94, P-value = 0.05). The association was also modified by ethanol intake from beer. A known functional SNP in ADH1B (rs1229984) was associated with alcohol intake (P-value = 0.04) but not GC risk. Variants in ADH7 were not associated with alcohol intake or GC risk. In conclusion, genetic variants at ADH1 and ALDH2 loci may influence GC risk, and alcohol intake may further modify the effect of ADH1 rs1230025. Additional population-based studies are needed to confirm our results.
U2 - 10.1093/carcin/bgr285
DO - 10.1093/carcin/bgr285
M3 - Article
C2 - 22144473
SN - 0143-3334
VL - 33
SP - 361
EP - 367
JO - Carcinogenesis
JF - Carcinogenesis
IS - 2
ER -
