酒精脱氢酶（ADH1A、ADH1B、ADH1C、ADH7）和乙醛脱氢酶（ALDH2）的遗传变异、饮酒与欧洲癌症前瞻性调查与营养队列（EPIC）中胃癌风险的关系。
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.
机构信息
Unit of Nutrition, Environment and Cancer, Epidemiology Research Program, Catalan Institute of Oncology (ICO-IDIBELL), Avda Gran Via 199-203, 08907 L'Hospitalet de Llobregat, Barcelona, Spain.
出版信息
Carcinogenesis. 2012 Feb;33(2):361-7. doi: 10.1093/carcin/bgr285. Epub 2011 Dec 5.
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 (OR(T v C) = 0.59; 95% CI = 0.38-0.91 and OR(T 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 (OR(A+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: OR(A) = 0.89, 95% CI = 0.57-1.39; ≥5 g/day: OR(A) = 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.
研究表明，饮酒与胃癌（GC）风险之间的关联并不一致。我们调查了酒精代谢基因座（乙醇脱氢酶，ADH1 基因簇：ADH1A、ADH1B 和 ADH1C；ADH7 和醛脱氢酶，ALDH2）中的 29 个遗传变异与酒精摄入和 GC 风险之间的关系。我们分析了欧洲癌症前瞻性调查和营养队列内嵌套病例对照研究（364 例病例和 1272 例对照）的数据。使用定制的基因芯片对单核苷酸多态性（SNP）进行了基因分型。我们观察到 ADH1A 附近的常见 3'侧翼 SNP（rs1230025）与 GC 风险之间存在统计学显著关联[等位基因比值比（OR）（A 对 T）=1.30，95%置信区间（CI）=1.07-1.59]。两个内含子变异，一个在 ADH1C（rs283411），一个在 ALDH2（rs16941667），也与 GC 风险相关（OR（T 对 C）=0.59；95%CI=0.38-0.91 和 OR（T 对 C）=1.34；95%CI=1.00-1.79，分别）。同时携带 ADH1（rs1230025）和 ALDH2（rs16941667）变异等位基因的个体发生 GC 的可能性是不携带变异等位基因的个体的两倍（OR（A+T）=2.0；95%CI=1.25-3.20）。rs1230025 与 GC 的关联受酒精摄入量的影响（<5 g/天：OR（A）=0.89，95%CI=0.57-1.39；≥5 g/天：OR（A）=1.45，95%CI=1.08-1.94，P 值=0.05）。该关联还受到啤酒中乙醇摄入的影响。ADH1B 中的一个已知功能 SNP（rs1229984）与酒精摄入量相关（P 值=0.04），但与 GC 风险无关。ADH7 中的变异与酒精摄入或 GC 风险无关。总之，ADH1 和 ALDH2 基因座的遗传变异可能影响 GC 风险，而酒精摄入可能进一步改变 ADH1 rs1230025 的作用。需要进行更多的基于人群的研究来证实我们的结果。
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