Increased cancer risk in heavy drinkers with the alcohol dehydrogenase 1C*1 allele, possibly due to salivary acetaldehyde
Increased cancer risk in heavy drinkers with the alcohol dehydrogenase 1C*1 allele, possibly due to salivary acetaldehyde
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携带酒精脱氢酶 1C*1 等位基因的酗酒者患癌症的风险增加，可能是由于唾液乙醛所致
作者：
J. Visapää;K. Götte;M. Benešová;J. Li;N. Homann;C. Conradt;H. Inoue;M. Tisch;K. Hörrmann;S. Väkeväinen;M. Salaspuro;H. Seitz
背景：长期饮酒与上呼吸消化道癌症风险增加有关。由于乙醛似乎是与慢性饮酒相关的致癌因素，具有乙醇脱氢酶（ADH）1C*1等位基因的酗酒者似乎特别危险，因为该等位基因编码快速乙醇代谢酶，导致乙醛水平升高。最近的流行病学研究结果相互矛盾，因此我们只调查了重度酒精消费者的ADH 1C基因型。研究方法：我们分析了107名患有上呼吸消化道癌症的重度饮酒者和103名年龄匹配的饮酒量相似的无癌症酒精对照者的ADH 1C基因型。采用基于限制性片段长度多态性方法的聚合酶链反应对白细胞DNA进行ADH 1C位点的基因分型。此外，21名ADH 1C * 1，1、ADH 1C * 1，2和ADH 1C * 2，2基因型的健康志愿者口服乙醇（0.3 g/kg体重），12名ADH基因型不同的志愿者随意饮用乙醇（平均211（29）g）。随后，通过气相色谱法或高效液相色谱法测量唾液乙醛浓度。结果如下：与年龄匹配的无癌症酒精对照组相比，患有上呼吸消化道癌症的重度饮酒者的ADH 1C *1等位基因频率显著增加（61.7%对49.0%; p = 0.011）。所有癌症病例与所有酒精对照组的未校正和校正比值比分别为1.67和1.69。ADH 1C *1等位基因纯合子的健康志愿者摄入酒精后唾液乙醛浓度高于ADH 1C杂合子（p = 0.056）或ADH 1C *2纯合子（p = 0.011）志愿者。 结论：这些数据表明，ADH 1C *1等位基因纯合子的重度饮酒者有发生上呼吸消化道癌的倾向，可能是由于饮酒后唾液乙醛水平升高。
Background: Chronic ethanol consumption is associated with an increased risk of upper aerodigestive tract cancer. As acetaldehyde seems to be a carcinogenic factor associated with chronic alcohol consumption, alcoholics with the alcohol dehydrogenase (ADH) 1C*1 allele seem to be particularly at risk as this allele encodes for a rapidly ethanol metabolising enzyme leading to increased acetaldehyde levels. Recent epidemiological studies resulted in contradictory results and therefore we have investigated ADH1C genotypes in heavy alcohol consumers only. Methods: We analysed the ADH1C genotype in 107 heavy drinkers with upper aerodigestive tract cancer and in 103 age matched alcoholic controls without cancer who consumed similar amounts of alcohol. Genotyping of the ADH1C locus was performed using polymerase chain reaction based on restriction fragment length polymorphism methods on leucocyte DNA. In addition, ethanol was administered orally (0.3 g/kg body weight) to 21 healthy volunteers with the ADH1C*1,1, ADH1C*1,2, and ADH1C*2,2 genotypes, and 12 volunteers with various ADH genotypes consumed ethanol ad libitum (mean 211 (29) g). Subsequently, salivary acetaldehyde concentrations were measured by gas chromatography or high performance liquid chromatography. Results: The allele frequency of the ADH1C*1 allele was found to be significantly increased in heavy drinkers with upper aerodigestive tract cancer compared with age matched alcoholic controls without cancer (61.7% v 49.0%; p = 0.011). The unadjusted and adjusted odds ratios for all cancer cases versus all alcoholic controls were 1.67 and 1.69, respectively. Healthy volunteers homozygous for the ADH1C*1 allele had higher salivary acetaldehyde concentrations following alcohol ingestion than volunteers heterozygous for ADH1C (p = 0.056) or homozygous for ADH1C*2 (p = 0.011). Conclusions: These data demonstrate that heavy drinkers homozygous for the ADH1C*1 allele have a predisposition to develop upper aerodigestive tract cancer, possibly due to elevated salivary acetaldehyde levels following alcohol consumption.
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酒精与癌症。
影响因子：
--
作者：
Rogers,AE;Conner,MW
通讯作者：
Conner,MW
影响因子：
2.9
作者：
Matsuda, T;Terashima, I;Shibutani, S
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DOI：
--
发表时间：
2001
期刊：
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
影响因子：
--
作者：
Sturgis,EM;Dahlstrom,KR;Guan,Y;Eicher,SA;Strom,SS;Spitz,MR;Wei,Q
通讯作者：
Wei,Q
头颈癌的风险和乙醇脱氢酶 3 基因型。
影响因子：
4.7
作者：
Olshan,AF;Weissler,MC;Watson,MA;Bell,DA
通讯作者：
Bell,DA