Shields P G, Harris C C
Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
JAMA. 1991 Aug 7;266(5):681-7.
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.
环境、职业和娱乐活动中接触致癌物会增加人类患癌风险。癌症形成是一个多阶段过程，包括肿瘤起始、促进、转化和进展。致癌物可通过遗传和表观遗传机制影响这些阶段中的任何一个。可疑致癌暴露与癌症风险之间的关联可以用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体风险评估。相比之下，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学有效剂量。分子流行病学还探索宿主癌症易感性，如致癌物代谢激活、DNA修复、内源性突变率以及突变肿瘤抑制基因的遗传。已经表明这些生物学终点中的每一个都存在很大的个体间差异，因此突出了个体层面评估癌症风险的必要性。鉴于过去十年的发展速度，未来十年分子流行病学家为个体制定包括多种因素评估的癌症风险概况是可行的。这将有助于聚焦预防策略并加强定量风险评估。
