Shortened telomeres in individuals with abuse in alcohol consumption.
Shortened telomeres in individuals with abuse in alcohol consumption.
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DOI：
10.1002/ijc.25999
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发表时间：
2011-08-15
影响因子：
6.4
通讯作者：
Baccarelli, Andrea
中科院分区：
文献类型：
--
作者：
Pavanello, Sofia;Hoxha, Mirjam;Dioni, Laura;Bertazzi, Pier Alberto;Snenghi, Rossella;Nalesso, Alessandro;Ferrara, Santo Davide;Montisci, Massimo;Baccarelli, Andrea
酗酒会导致与衰老有关的疾病，包括多部位癌症的早期发病。外周血白细胞（PBL）中较短的端粒长度（TL）是生物衰老的标志，与酒精相关的癌症风险有关。酒精滥用者是否表现出加速的生物衰老，如PBL-TL所反映的，从未被研究过。为了研究酒精滥用对PBL-TL的影响及其与酒精代谢基因型的相互作用，我们检查了200名根据精神疾病诊断和统计手册[DSM-IV-TR]诊断为酒精滥用者的酒后驾车交通违法者，并参加了缓刑计划，以及257名社交饮酒者（对照）。我们使用自我报告的饮酒单位/天和传统的酒精滥用生物标志物（血清γ-谷氨酰转移酶[GGT]和红细胞平均体积[MCV]）评估酒精摄入量。我们使用多变量模型计算TL几何平均值（GM），校正了年龄、吸烟、BMI、饮食、事故高风险工作、遗传毒性暴露。与对照组相比，酒精滥用者的TL几乎减半（GMs 0.42 vs. 0.87相对T/S比率; P<0.0001），并且随着每天饮酒单位的增加而降低（P趋势=0.003）。饮酒量>4个单位/天的个体的TL显著短于饮酒量为4个单位/天的个体（GM 0.48 vs. 0.61 T/S，P=0.002）。携带常见ADH 1B *1/*1（rs 1229984）基因型的人更有可能成为滥用者（P=0.008），报告更高的饮酒单位/天（P=0.0003），并表现出更短的TL（P<0.0001）。rs698 ADH 1C和rs671 ALDH 2多态性与TL无关。酒精代谢基因型ADH 1B *1/*1调节的PBL-TL减少可能代表了一种与酒精滥用者酒精致癌潜在相关的新机制。
Alcohol abuse leads to earlier onset of aging-related diseases, including cancer at multiple sites. Shorter telomere length (TL) in peripheral blood leucocytes (PBLs), a marker of biological aging, has been associated with alcohol-related cancer risks. Whether alcohol abusers exhibit accelerated biological aging, as reflected in PBL-TL, has never been examined. To investigated the effect of alcohol abuse on PBL-TL and its interaction with alcohol metabolic genotypes, we examined 200 drunk-driving traffic offenders diagnosed as alcohol abusers as per the Diagnostic and Statistical Manual of Mental Disorders [DSM-IV-TR] and enrolled in a probation program, and 257 social drinkers (controls). We assessed alcohol intake using self-reported drink-units/day and conventional alcohol abuse biomarkers (serum γ-glutamyltrasferase [GGT] and mean corpuscular volume of erythrocytes [MCV]). We used multivariable models to compute TL geometric means (GM) adjusted for age, smoking, BMI, diet, job at elevated risk of accident, genotoxic exposures. TL was nearly halved in alcohol abusers compared to controls (GMs 0.42 vs. 0.87 relative T/S ratio; P<0.0001) and decreased in relation with increasing drink-units/day (P-trend=0.003). Individuals drinking >4 drink-units/day had substantially shorter TL than those drinking 4 drink-units/day (GMs 0.48 vs. 0.61 T/S, P=0.002). Carriers of the common ADH1B*1/*1 (rs1229984) genotype were more likely to be abusers (P=0.008), reported higher drink-units/day (P=0.0003), and exhibited shorter TL (P<0.0001). The rs698 ADH1C and rs671 ALDH2 polymorphisms were not associated with TL. The decrease in PBL-TL modulated by the alcohol metabolic genotype ADH1B*1/*1 may represent a novel mechanism potentially related to alcohol carcinogenesis in alcohol abusers.
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