期刊
CARCINOGENESIS
卷 33, 期 2, 页码 361-367出版社
OXFORD UNIV PRESS
DOI: 10.1093/carcin/bgr285
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资金
- European Commission (DG-SANCO)
- International Agency for Research on Cancer
- Spanish Ministry of Health [P10710130]
- Regional Governments of Andalucia, Asturias, Basque Country, Murcia [6236]
- Navarra and the Catalan Institute of Oncology, La Caixa (Spain) [BM 06-130, RTICC-RD06/0020]
- Danish Cancer Society (Denmark)
- Ligue contre le Cancer
- Institut Gustave Roussy
- Mutuelle Generale de l'Education Nationale
- Institut National de la Sante et de la Recherche Medicale (INSERM) (France)
- Deutsche Krebshilfe
- Deutsches Krebsforschungszentrum
- Federal Ministry of Education and Research (Germany)
- Hellenic Health Foundation
- Stavros Niarchos Foundation
- Hellenic Ministry of Health and Social Solidarity (Greece)
- Italian Association for Research on Cancer (AIRC)
- National Research Council (Italy)
- Dutch Ministry of Public Health, Welfare and Sports (VWS)
- Netherlands Cancer Registry (NKR)
- LK Research Funds
- Dutch Prevention Funds
- Dutch ZON (Zorg Onderzoek Nederland)
- World Cancer Research Fund (WCRF)
- Statistics Netherlands (The Netherlands)
- Norwegian Cancer Society (Norway)
- Swedish Cancer Society
- Swedish Scientific Council
- Regional Government of Skane and Vasterbotten (Sweden)
- Cancer Research UK
- Medical Research Council (United Kingdom)
- Medical Research Council [G0401527, G0801056B, MC_U106179471, G1000143] Funding Source: researchfish
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.
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