Department of Environmental Medicine and Public Health, Occupational Health Section, Università di Padova, Via Giustiniani 2, 35128 Padova, Italy.
Int J Cancer. 2011 Aug 15;129(4):983-92. doi: 10.1002/ijc.25999. Epub 2011 Apr 25.
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 with 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 ADH1B1/*1 may represent a novel mechanism potentially related to alcohol carcinogenesis in alcohol abusers.
酗酒会导致与衰老相关的疾病更早发作，包括多个部位的癌症。外周血白细胞（PBL）中端粒长度（TL）较短，这是生物衰老的标志，与酒精相关的癌症风险有关。酗酒者是否表现出生物衰老加速，如 PBL-TL 所反映的那样，尚未得到检验。为了研究酗酒对 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 名被诊断为酗酒者的醉酒驾驶交通违法者，并将他们纳入缓刑计划，以及 257 名社交饮酒者（对照组）。我们使用自我报告的饮酒单位/天和常规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]）来评估酒精摄入量。我们使用多变量模型计算经过年龄、吸烟、BMI、饮食、易发生事故的工作、遗传毒性暴露调整后的 TL 几何平均值（GM）。与对照组相比，酗酒者的 TL 几乎减半（相对 T/S 比的 GM 为 0.42 对 0.87；p<0.0001），并且与饮酒量的增加呈负相关（p 趋势=0.003）。每天饮酒量>4 单位的个体的 TL 明显短于每天饮酒量≤4 单位的个体（相对 T/S 的 GMs 为 0.48 对 0.61，p=0.002）。常见 ADH1B*1/1（rs1229984）基因型的携带者更有可能成为酗酒者（p=0.008），报告的饮酒量更高（p=0.0003），并且 TL 更短（p<0.0001）。rs698 ADH1C 和 rs671 ALDH2 多态性与 TL 无关。ADH1B1/*1 酒精代谢基因型调节的 PBL-TL 下降可能代表一种潜在与酗酒者酒精致癌作用相关的新机制。
