Ann ICRP. 1998;28(1-2):1-157.
A Task Group of the ICRP Committee 1 (Radiation Effects) has reviewed relevant data with the objective of advising the Main Commission of the ICRP on the possible implications for radiological protection of emerging views on genetic susceptibility to cancer (Chapter 1). Chapter 2 considers DNA damage and its processing/repair after ionising radiation and serves principally to demonstrate that a few rare cancer-prone, human recessive genetic disorders show DNA repair deficiency and profound increases in radiosensitivity. Less dramatic changes in radiosensitivity are also apparent in a wider range of such disorders. The cellular mechanisms that underly the association between DNA damage processing and tumorigenesis are discussed. Chapter 3 reviews the mechanisms and genetics of solid tumours illustrating the ways in which mutations in proto-oncogenes, tumour suppressor genes together with those in DNA repair and cell cycle control genes can contribute to tumour development. Specific examples are given of how germ line mutation of such genes can predispose to familial cancer. It is judged that up to 5% of all solid tumours have a recognisable genetic component. Heritable organ-specific effects are most usual and cancers of the breast and colon tend to show the most obvious genetic components. Clearly discernible genetic effects are seen when rare dominant germ line mutations express strongly as familial cancer (high penetrance mutations), but the existence of perhaps less rare low penetrance mutations and gene-gene interactions are recognised but not well understood. Chapter 4 considers the mechanisms and genetics of lympho-haemopoietic tumours. Specific chromosomal translocations and proto-oncogene activation events are much more frequent in human leukaemia/lymphoma than in solid tumours. Genetic predisposition to leukaemia/lymphoma is found in a number of non-familial recessive genetic disorders of DNA processing and/or chromosomal instability. Familial manifestation of susceptibility to these tumours is, however, extremely rare. The genetic component, although poorly defined, is judged to be less than that of solid tumours and expressed largely in childhood. Chapter 5 reviews and discusses limited data that comment upon tumorigenic radiosensitivity in cancer-prone genetic conditions. From knowledge of the fundamental processes involved it is judged that in most, but not all, cases genetic susceptibility to spontaneous tumours will be accompanied by a greater-than-normal risk after radiation. A review of epidemiological, clinical and experimental data relevant to this issue suggests that although a wide range of different sensitivities may be involved, a factor of 10 increase in sensitivity broadly accords with the limited human data available. This interim judgement of a factor of 10 increase in radiation risk in such human genetic disorders is made for the purposes of illustrative modelling and calculation. In addition, specific attention is given to breast cancer risk in heterozygotes for the radiosensitive human disorder, ataxia-telangiectasia; this association, while in no way discounted, is judged to be less strong than that claimed by some. Chapter 6 discusses and develops computational modelling procedures that aim to describe the impact of genetic factors on radiation-tumorigenesis in human populations. Estimates of the prevalence of known cancer-prone genetic disorders are made but breast cancer susceptibility is used to illustrate the application of the model developed. The most important message to emerge from this work is that, even at an assumed high level of radiation sensitivity, the prevalence of familial (high penetrance) genetic disorders in the population is too low (<1%) for there to be a significant impact on risk in typical human populations. In principle, however, there is the potential for such impact in atypical inbred sub-populations where these mutations can be more common. (ABSTRACT TRUNCATED)
国际放射防护委员会第1委员会（辐射效应）的一个特别工作组审查了相关数据，目的是就癌症遗传易感性的新观点对放射防护可能产生的影响向国际放射防护委员会主要委员会提供建议（第1章）。第2章考虑了电离辐射后的DNA损伤及其处理/修复，主要是为了证明一些罕见的、易患癌症的人类隐性遗传疾病表现出DNA修复缺陷和辐射敏感性的显著增加。在更广泛的此类疾病中，辐射敏感性也有不太明显的变化。讨论了DNA损伤处理与肿瘤发生之间关联的细胞机制。第3章回顾了实体瘤的机制和遗传学，阐述了原癌基因、肿瘤抑制基因以及DNA修复和细胞周期控制基因中的突变如何促进肿瘤发展。给出了此类基因的种系突变如何导致家族性癌症的具体例子。据判断，所有实体瘤中高达5%具有可识别的遗传成分。可遗传的器官特异性效应最为常见，乳腺癌和结肠癌往往表现出最明显的遗传成分。当罕见的显性种系突变强烈表现为家族性癌症（高外显率突变）时，可以看到明显的遗传效应，但人们认识到可能存在不太罕见的低外显率突变和基因-基因相互作用，只是对此了解不多。第4章考虑了淋巴造血肿瘤的机制和遗传学。特定的染色体易位和原癌基因激活事件在人类白血病/淋巴瘤中比在实体瘤中更为常见。在一些DNA处理和/或染色体不稳定的非家族性隐性遗传疾病中发现了白血病/淋巴瘤的遗传易感性。然而，这些肿瘤易感性的家族表现极为罕见。遗传成分虽然定义不明确，但据判断比实体瘤的遗传成分要少，且主要在儿童期表现出来。第5章回顾并讨论了关于癌症易感遗传条件下致瘤辐射敏感性的有限数据。根据所涉及的基本过程的知识判断，在大多数但并非所有情况下，对自发肿瘤的遗传易感性在辐射后将伴随着高于正常的风险。对与此问题相关的流行病学、临床和实验数据的回顾表明，尽管可能涉及广泛的不同敏感性，但敏感性增加10倍大致符合现有的有限人类数据。为了说明性建模和计算的目的，对这类人类遗传疾病中辐射风险增加10倍的这一临时判断。此外，特别关注了对辐射敏感的人类疾病共济失调-毛细血管扩张症杂合子患乳腺癌的风险；这种关联虽然绝不能忽视，但据判断比一些人声称的要弱。第6章讨论并开发了计算建模程序，旨在描述遗传因素对人群中辐射致瘤的影响。对已知的癌症易感遗传疾病的患病率进行了估计，但以乳腺癌易感性为例说明了所开发模型的应用。这项工作得出的最重要信息是，即使在假定的高辐射敏感性水平下，人群中家族性（高外显率）遗传疾病的患病率也太低（<1%），以至于对典型人群的风险没有显著影响。然而，原则上，在这些突变可能更常见的非典型近亲亚人群中存在这种影响的可能性。（摘要截断）
