Wang J S, Qian G S, Zarba A, He X, Zhu Y R, Zhang B C, Jacobson L, Gange S J, Muñoz A, Kensler T W
Department of Environmental Health Sciences, School of Hygiene and Public Health, Johns Hopkins University, Baltimore, Maryland 21205, USA.
Cancer Epidemiol Biomarkers Prev. 1996 Apr;5(4):253-61.
Molecular epidemiological studies of populations at high risk for liver cancer have shown that hepatitis B virus (HBV) and aflatoxin B1 (AFB1) exposure are two major risk factors for this disease. These etiological agents, combined with nutritional deficiencies, are important for the initiation and promotion of liver cancer in various parts of the world. In Qidong, People's Republic of China, liver cancer accounts for 10% of all adult deaths, and both HBV and AFB1 exposures are common. To study temporal and possible chemical-viral interactions in people, serum samples were collected during a longitudinal study designed to measure aflatoxin molecular biomarkers in residents of Daxin Township, Qidong City, People's Republic of China. In this study, the temporal modulation of aflatoxin adduct formation with albumin over multiple lifetimes of serum albumin was examined in both HBV-positive and HBV-negative people in two periods: September-December 1993 (wave 1) and June-September 1994 (wave 2). During the 12-week monitoring period of wave 1, 120 individuals (balanced by gender and HBV status) provided a total of 792 blood samples. AFB1-albumin adducts were detected in all but one of the serum samples. The range of binding detected by RIA in the Daxin population was 0.17-4.39 pmol AFB11/mg albumin with an overall mean +/- SD of 1.51 +/- 0.21 pmol AFB11/mg albumin. The mean +/- SD for weeks 0, 2, 4, 6, 8, 10 and 12 of wave 1 were 1.21 +/- 0.41, 1.58 +/- 0.70, 1.36 +/- 0.52, 1.71 +/- 0.44, 1.18 +/- 0.60, 2.00 +/- 0.59, and 1.68 +/- 0.34 pmol AFB1/mg albumin, respectively. During wave 2, 103 individuals from wave 1 provided a total of 396 blood samples collected monthly over wave 2, with mean +/- SD aflatoxin-albumin adduct levels of 1.19 +/- 0.37, 0.85 +/- 0.45, 0.89 +/- 0.28, and 0.61 +/- 0.15 pmol AFB1/mg albumin. Using linear regression models, the mean aflatoxin-albumin adduct levels increased (P < 0.05) during the 12 weeks of wave 1 and decreased (P < 0.05) over the 4 months of wave 2. Neither HBV surface antigen status nor gender modified either the baseline mean or the temporal trend. High-performance liquid chromatography confirmation was done on a subset of serum samples, and the results show an excellent association between the immunoassay data and high-performance liquid chromatography. Taken together, these data demonstrate that AFB1-albumin is a sensitive and specific biomarker for assessing exposure to this carcinogen in the population in Qidong.
对肝癌高危人群的分子流行病学研究表明,乙型肝炎病毒(HBV)感染和黄曲霉毒素B1(AFB1)暴露是导致该病的两个主要危险因素。这些致病因素,再加上营养缺乏,在世界不同地区对肝癌的发生和发展起着重要作用。在中国启东,肝癌占成人死亡总数的10%,HBV感染和AFB1暴露都很常见。为了研究人群中的时间变化以及可能存在的化学 - 病毒相互作用,在一项纵向研究中收集了血清样本,该研究旨在测量中国启东市大兴镇居民体内的黄曲霉毒素分子生物标志物。在这项研究中,对1993年9月至12月(第1波)和1994年6月至9月(第2波)这两个时间段内HBV阳性和HBV阴性人群血清白蛋白多个生命周期中黄曲霉毒素加合物形成的时间变化情况进行了检测。在第1波为期12周的监测期内,120名个体(按性别和HBV状态均衡分组)共提供了792份血样。除一份血清样本外,其余所有样本均检测到AFB1 - 白蛋白加合物。用放射免疫分析法(RIA)检测到大兴镇人群中加合物的结合范围为0.17 - 4.39 pmol AFB11/mg白蛋白,总体平均水平±标准差为1.51±0.21 pmol AFB11/mg白蛋白。第1波第0、2、4、6、8、10和12周的平均水平±标准差分别为1.21±0.41、1.58±0.70、1.36±0.52、1.71±0.44、1.18±0.60、2.00±0.59和1.68±0.34 pmol AFB1/mg白蛋白。在第2波期间,第1波中的103名个体共提供了396份血样,在第2波期间每月采集一次,黄曲霉毒素 - 白蛋白加合物平均水平±标准差分别为1.19±0.37、0.85±0.45、0.89±0.28和0.61±0.15 pmol AFB1/mg白蛋白。使用线性回归模型分析发现,第1波的12周内黄曲霉毒素 - 白蛋白加合物平均水平升高(P < 0.05),而第2波的4个月内则降低(P < 0.05)。HBV表面抗原状态和性别均未改变基线平均值或时间变化趋势。对一部分血清样本进行了高效液相色谱法验证,结果表明免疫分析数据与高效液相色谱法之间具有良好的相关性。综上所述,这些数据表明AFB1 - 白蛋白是评估启东人群中该致癌物暴露情况的一种敏感且特异的生物标志物。