Wild C P, Yin F, Turner P C, Chemin I, Chapot B, Mendy M, Whittle H, Kirk G D, Hall A J
Molecular Epidemiology Unit, School of Medicine, University of Leeds, UK.
Int J Cancer. 2000 Apr 1;86(1):1-7. doi: 10.1002/(sici)1097-0215(20000401)86:1<1::aid-ijc1>3.0.co;2-i.
Aflatoxins together with chronic hepatitis B virus (HBV) infection contribute to the high incidence of hepatocellular carcinoma in developing countries. An understanding of the mechanism of interaction between these factors would provide a strong rationale for developing effective prevention strategies. In this study in The Gambia we examined the effect of environmental (place of residence and timing of sample collection) and host factors (age, sex, HBV status and interindividual variations in carcinogen metabolising enzymes) in determining blood aflatoxin-albumin adduct levels in 357 individuals of whom 181 were chronic HBV carriers. Samples were analysed for aflatoxin-albumin adducts, HBV status and genotypes of glutathione S-transferase (GST) M1, GSTT1, GSTP1 and epoxide hydrolase (EPXH). Urine samples were analysed for 6beta-hydroxycortisol:cortisol ratio as a marker of cytochrome P450 (CYP) 3A4 activity. Adduct levels were significantly higher in subjects resident in rural [geometric mean adduct level 34.9 pg aflatoxin B1-lysine equivalent (28.5-42.8; 95%CI)/mg albumin] than in periurban areas [22.2 pg (14.9-33.4)/mg] and were approximately twice as high in the dry season [mid-February to March; 83.2 pg (53.3-130.8)/mg] than the wet [July to August; 34.9 pg (28.5-42.8)/mg]. In contrast, HBV status, CYP3A4 phenotype, GSTT1, GSTP1 and EPXH genotypes were not associated with aflatoxin-albumin adduct level. However, mean adduct levels were significantly higher in non-HBV infected subjects with GSTM1 null genotype. The main factors which affect aflatoxin-albumin adduct levels in this population are environmental, notably place of residence and timing of sample collection. This study further emphasises the priority to reduce aflatoxin exposure in these communities by primary prevention measures.
黄曲霉毒素与慢性乙型肝炎病毒（HBV）感染共同导致了发展中国家肝细胞癌的高发病率。了解这些因素之间的相互作用机制将为制定有效的预防策略提供有力依据。在冈比亚的这项研究中，我们调查了环境因素（居住地和样本采集时间）和宿主因素（年龄、性别、HBV感染状况以及致癌物代谢酶的个体差异）对357名个体血液中黄曲霉毒素 - 白蛋白加合物水平的影响，其中181人是慢性HBV携带者。对样本进行了黄曲霉毒素 - 白蛋白加合物、HBV感染状况以及谷胱甘肽S - 转移酶（GST）M1、GSTT1、GSTP1和环氧化物水解酶（EPXH）基因型的分析。对尿液样本进行了6β - 羟基皮质醇：皮质醇比值分析，作为细胞色素P450（CYP）3A4活性的标志物。农村居民的加合物水平显著高于城郊地区[几何平均加合物水平为34.9 pg黄曲霉毒素B1 - 赖氨酸当量（28.5 - 42.8；95%置信区间）/mg白蛋白]，分别为[22.2 pg（14.9 - 33.4）/mg]，并且旱季[2月中旬至3月；83.2 pg（53.3 - 130.8）/mg]的加合物水平大约是雨季[7月至8月；34.9 pg（28.5 - 42.8）/mg]的两倍。相比之下，HBV感染状况、CYP3A4表型、GSTT1、GSTP1和EPXH基因型与黄曲霉毒素 - 白蛋白加合物水平无关。然而，GSTM1基因缺失型的非HBV感染受试者的平均加合物水平显著更高。影响该人群黄曲霉毒素 - 白蛋白加合物水平的主要因素是环境因素，尤其是居住地和样本采集时间。这项研究进一步强调了通过一级预防措施减少这些社区黄曲霉毒素暴露的紧迫性。
