Smith Martyn T, Skibola Christine F, Allan James M, Morgan Gareth J
Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley 94720-7360, USA.
IARC Sci Publ. 2004(157):373-92.
In this chapter, we apply the molecular epidemiological paradigm of biomarkers of exposure, early effect and susceptibility to causal models of leukaemia and lymphoma. The aim is to enhance the development of biomarkers for use in studying the causes of these haematopoeitic cancers in the general population. Two causal models of acute myeloid leukaemia are discussed in detail: chemotherapy-induced and benzene-induced acute myeloid leukaemia. Specific chromosomal changes found in acute myeloid leukaemia may serve as useful biomarkers of early effect in these models, and genetic variants in glutathione S-transferases, NQO1 and DNA-repair enzymes may serve as useful biomarkers of susceptibility. Several causal models of lymphoma exist in which biomarkers could be developed and validated. These include human immunodeficiency virus (HIV) immunosuppression, families with inherited disorders and workers exposed to petroleum products, pesticides or organochlorines. Biomarkers of early effect could include markers of DNA double-strand breaks and aberrant V(D)J recombination, and susceptibility may be related to polymorphisms in genes controlling DNA repair and immunological status. We predict that biomarkers of susceptibility will continue to be studied in the case-control format, perhaps in large pooled studies, but that for biomarkers of early effect, there will be a move away from the study of diseased populations to the study of individuals 'at risk' in the causal models described above.
在本章中，我们将暴露、早期效应和易感性生物标志物的分子流行病学范式应用于白血病和淋巴瘤的因果模型。目的是加强生物标志物的开发，以用于研究普通人群中这些血液系统癌症的病因。详细讨论了急性髓系白血病的两种因果模型：化疗诱导的急性髓系白血病和苯诱导的急性髓系白血病。在这些模型中，急性髓系白血病中发现的特定染色体变化可能作为早期效应的有用生物标志物，而谷胱甘肽S-转移酶、NQO1和DNA修复酶中的基因变异可能作为易感性的有用生物标志物。存在几种淋巴瘤的因果模型，在这些模型中可以开发和验证生物标志物。这些包括人类免疫缺陷病毒（HIV）免疫抑制、患有遗传性疾病的家族以及接触石油产品、农药或有机氯的工人。早期效应的生物标志物可能包括DNA双链断裂和异常V（D）J重组的标志物，易感性可能与控制DNA修复和免疫状态的基因多态性有关。我们预测，易感性生物标志物将继续以病例对照形式进行研究，可能在大型汇总研究中进行，但对于早期效应生物标志物，将从患病群体的研究转向对上述因果模型中“有风险”个体的研究。
