MOLECULAR EPIDEMIOLOGY AND THE GENETICS OF ENVIRONMENTAL CANCER
MOLECULAR EPIDEMIOLOGY AND THE GENETICS OF ENVIRONMENTAL CANCER
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DOI：
10.1001/jama.266.5.681
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发表时间：
1991-08-07
影响因子：
120.7
通讯作者：
HARRIS, CC
中科院分区：
文献类型：
--
作者：
SHIELDS, PG;HARRIS, CC
环境、职业和娱乐暴露于致癌物会增加人类的癌症风险。癌症的形成是一个多阶段的过程，涉及肿瘤的起始、促进、转化和进展。致癌物可以通过遗传和表观遗传机制影响这些阶段中的任何一个。可疑致癌物暴露与癌症风险之间的关系可以通过经典流行病学技术在人群中进行研究。然而，这些技术不适用于个人风险评估。相反，分子流行病学是一个整合分子生物学、体外和体内实验室模型、生物化学和流行病学以推断个体癌症风险的领域。可以测量致癌物-大分子加合物水平和体细胞突变，以确定致癌物的生物有效剂量。分子流行病学还探索宿主癌症易感性，如致癌物质代谢活化，DNA修复，内源性突变率和突变的肿瘤抑制基因的遗传。这些生物学终点中的每一个都存在显著的个体间差异，因此，强调了在个体基础上评估癌症风险的必要性。考虑到过去十年的发展速度，未来十年将允许分子流行病学家为个体制定一个包括评估许多因素在内的癌症风险概况是可行的。这将有助于突出预防战略的重点，加强定量风险评估。
Environmental, occupational, and recreational exposures to carcinogens contribute to cancer risk in humans. Cancer formation is a multistage process involving tumor initiation, promotion, conversion, and progression. Carcinogens can affect any of these stages through genetic and epigenetic mechanisms. The association of a suspected carcinogenic exposure and cancer risk can be studied in populations with classic epidemiologic techniques. However, these techniques are not applicable to the assessment of risk in individuals. Molecular epidemiology, in contrast, is a field that integrates molecular biology, in vitro and in vivo laboratory models, biochemistry, and epidemiology to infer individual cancer risk. Carcinogen-macromolecular adduct levels, and somatic cell mutations can be measured to determine the biologically effective dose of a carcinogen. Molecular epidemiology also explores host cancer susceptibilities, such as carcinogen metabolic activation, DNA repair, endogenous mutation rates, and inheritance of mutated tumor suppressor genes. Substantial interindividual variation for each of these biologic end points has been shown and, therefore, highlights the need for assessing cancer risk on an individual basis. Given the pace of the last decade, it is feasible that the next 10 years will allow molecular epidemiologists to develop a cancer-risk profile for an individual that includes assessment of a number of factors. This will help focus preventive strategies and strengthen quantitative risk assessments.