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

被引：59

作者：

Duell, Eric J. ^{[1
]}

Sala, Nuria ^{[1
]}

Travier, Noemie ^{[1
]}

Munoz, Xavier ^{[1
]}

Christine Boutron-Ruault, Marie ^{[2
]}

Clavel-Chapelon, Francoise ^{[2
]}

Barricarte, Aurelio ^{[3
,4
]}

Arriola, Larraitz ^{[4
,5
]}

Navarro, Carmen ^{[4
,6
]}

Sanchez-Cantalejo, Emilio ^{[4
,7
]}

Ramon Quiros, J. ^{[8
]}

Krogh, Vittorio ^{[9
]}

Vineis, Paolo ^{[10
,11
]}

Mattiello, Amalia ^{[12
]}

Tumino, Rosario

Khaw, Kay-Tee ^{[13
]}

Wareham, Nicholas ^{[14
]}

Allen, Naomi E. ^{[15
]}

Peeters, Petra H. ^{[16
]}

Numans, Mattijs E. ^{[16
]}

Bueno-de-Mesquita, H. B. ^{[17
,18
]}

van Oijen, M. G. H. ^{[18
,19
]}

Bamia, Christina ^{[20
]}

Benetou, Vassiliki ^{[20
]}

Trichopoulos, Dimitrios ^{[21
,22
]}

Canzian, Federico ^{[23
]}

Kaaks, Rudolf ^{[24
]}

Boeing, Heiner ^{[25
]}

Bergmann, Manuela M. ^{[25
]}

Lund, Eiliv ^{[26
]}

Ehrnstrom, Roy ^{[27
,28
]}

Johansen, Dorthe ^{[29
]}

Hallmans, Goran ^{[30
]}

Stenling, Roger ^{[31
]}

Tjonneland, Anne ^{[32
]}

Overvad, Kim ^{[33
]}

Ostergaard, Jane Nautrup ^{[34
]}

Ferrari, Pietro ^{[35
]}

Fedirko, Veronika ^{[35
]}

Jenab, Mazda ^{[35
]}

Nesi, Gabriella ^{[36
]}

Riboli, Elio

Gonzalez, Carlos A. ^{[1
]}

机构：

[1] Catalan Inst Oncol ICO IDIBELL, Epidemiol Res Program, Unit Nutr Environm & Canc, Barcelona 08907, Spain

[2] Paris S Univ, INSERM, Ctr Res Epidemiol & Populat Hlth, Inst Gustave Roussy, Villejuif, France

[3] Navarre Publ Hlth Inst, Pamplona 31003, Spain

[4] CIBERESP, Consortium Biomed Res Epidemiol & Publ Hlth, Madrid 28029, Spain

[5] Basque Govt, Publ Hlth Dept Gipuzkoa, San Sebastian 20013, Spain

[6] Murcia Reg Hlth Author, Dept Epidemiol, Murcia 30008, Spain

[7] Andalusian Sch Publ Hlth, Granada 18018, Spain

[8] Hlth & Hlth Care Serv Council, Asturias 33001, Spain

[9] Fdn IRCCS Ist Nazl Tumori, Nutr Epidemiol Unit, I-20133 Milan, Italy

[10] Univ London Imperial Coll Sci Technol & Med, Ctr Environm & Hlth, Sch Publ Hlth, London SW7 2AZ, England

[11] HuGeF Fdn, I-10126 Turin, Italy

[12] Univ Naples Federico 2, Dept Clin & Expt Med, I-80138 Naples, Italy

[13] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge CB2 1TN, England

[14] Addenbrookes Hosp, Inst Metab Sci, MRC Epidemiol Unit, Cambridge CB2 0QQ, England

[15] Univ Oxford, Canc Epidemiol Unit, Oxford OX1 2JD, England

[16] Univ Ctr Utrecht, Julius Ctr, NL-3508 GA Utrecht, Netherlands

[17] Natl Inst Publ Hlth & Environm RIVM, NL-3720 BA Bilthoven, Netherlands

[18] Univ Med Ctr Utrecht, Dept Gastroenterol & Hepatol, NL-3508 GA Utrecht, Netherlands

[19] Univ Med Ctr Utrecht, Ctr Hlth Sci & Primary Care, NL-3508 GA Utrecht, Netherlands

[20] Univ Athens, Sch Med, WHO Collaborating Ctr Food & Nutr Policies, Dept Hyg Epidemiol & Med Stat, Athens 10679, Greece

[21] Harvard Univ, Dept Epidemiol, Sch Publ Hlth, Boston, MA 02115 USA

[22] Acad Athens, Bur Epidemiol Res, Athens 10679, Greece

[23] German Canc Res Ctr, Genom Epidemiol Grp, D-69120 Heidelberg, Germany

[24] German Canc Res Ctr, Div Canc Epidemiol, D-69120 Heidelberg, Germany

[25] German Inst Human Nutr, Dept Epidemiol, D-14558 Potsdam, Germany

[26] Univ Tromso, Dept Community Med, N-9037 Tromso, Norway

[27] Skane Univ Hosp, Univ & Reg Labs Region Skane, SE-20502 Malmo, Sweden

[28] Skane Univ Hosp, Dept Pathol, SE-20502 Malmo, Sweden

[29] Skane Univ Hosp, Dept Surg, SE-20502 Malmo, Sweden

[30] Umea Univ, Dept Publ Hlth & Clin Med, SE-90187 Umea, Sweden

[31] Umea Univ, Dept Med Biosci, SE-90187 Umea, Sweden

[32] Danish Canc Soc, Inst Canc Epidemiol, DK-2100 Copenhagen, Denmark

[33] Aarhus Univ, Dept Epidemiol, Sch Publ Hlth, DK-8000 Aarhus, Denmark

[34] Aarhus Univ Hosp, Dept Cardiol, Cardiovasc Res Ctr, Aalborg Hosp, DK-8000 Aalborg, Denmark

[35] WHO, Int Agcy Res Canc, F-69372 Lyon, France

[36] Univ Florence, Div Anat Pathol, I-50121 Florence, Italy

来源：

CARCINOGENESIS | 2012年 / 33卷 / 02期

基金：

英国医学研究理事会;

关键词：

HELICOBACTER-PYLORI; ESOPHAGEAL CANCER; POLYMORPHISMS; METAANALYSIS; METABOLISM; ADENOCARCINOMA; ACETALDEHYDE; ASSOCIATIONS; POPULATIONS; DEPENDENCE;

D O I：

10.1093/carcin/bgr285

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：361 / 367

页数：7

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