Department of Epidemiology and Biostatistics, Imperial College School of Public Health, Faculty of Medicine, St Mary's Campus, Norfolk Place, London W2 1PG, UK.
Mutat Res. 2010 May 1;687(1-2):17-27. doi: 10.1016/j.mrfmmm.2010.01.008. Epub 2010 Jan 25.
In this paper we review the evidence for departure from linearity for malignant and non-malignant disease and in the light of this assess likely mechanisms, and in particular the potential role for non-targeted effects. Excess cancer risks observed in the Japanese atomic bomb survivors and in many medically and occupationally exposed groups exposed at low or moderate doses are generally statistically compatible. For most cancer sites the dose-response in these groups is compatible with linearity over the range observed. The available data on biological mechanisms do not provide general support for the idea of a low dose threshold or hormesis. This large body of evidence does not suggest, indeed is not statistically compatible with, any very large threshold in dose for cancer, or with possible hormetic effects, and there is little evidence of the sorts of non-linearity in response implied by non-DNA-targeted effects. There are also excess risks of various types of non-malignant disease in the Japanese atomic bomb survivors and in other groups. In particular, elevated risks of cardiovascular disease, respiratory disease and digestive disease are observed in the A-bomb data. In contrast with cancer, there is much less consistency in the patterns of risk between the various exposed groups; for example, radiation-associated respiratory and digestive diseases have not been seen in these other (non-A-bomb) groups. Cardiovascular risks have been seen in many exposed populations, particularly in medically exposed groups, but in contrast with cancer there is much less consistency in risk between studies: risks per unit dose in epidemiological studies vary over at least two orders of magnitude, possibly a result of confounding and effect modification by well known (but unobserved) risk factors. In the absence of a convincing mechanistic explanation of epidemiological evidence that is, at present, less than persuasive, a cause-and-effect interpretation of the reported statistical associations for cardiovascular disease is unreliable but cannot be excluded. Inflammatory processes are the most likely mechanism by which radiation could modify the atherosclerotic disease process. If there is to be modification by low doses of ionizing radiation of cardiovascular disease through this mechanism, a role for non-DNA-targeted effects cannot be excluded.
本文回顾了恶性和非恶性疾病偏离线性的证据，并根据这些证据评估了可能的机制，特别是非靶向效应的潜在作用。在日本原子弹幸存者和许多接受低剂量或中剂量医学和职业照射的人群中观察到的过量癌症风险通常在统计学上是一致的。对于大多数癌症部位，这些人群的剂量-反应与观察到的范围内的线性一致。关于生物学机制的现有数据并没有普遍支持低剂量阈值或兴奋效应的观点。大量证据不支持癌症存在很大的剂量阈值或可能的兴奋效应，也没有证据表明存在非 DNA 靶向效应所暗示的那种反应非线性。日本原子弹幸存者和其他人群中也存在各种非恶性疾病的超额风险。特别是，在原子弹数据中观察到心血管疾病、呼吸道疾病和消化系统疾病的风险增加。与癌症不同，在各种暴露人群之间，风险模式的一致性要差得多；例如，在这些其他（非原子弹）人群中没有观察到与辐射相关的呼吸道和消化系统疾病。在许多暴露人群中都观察到心血管风险，特别是在医学暴露人群中，但与癌症不同的是，研究之间的风险一致性要差得多：在流行病学研究中，每单位剂量的风险变化至少跨越两个数量级，这可能是由于众所周知（但未观察到）的风险因素的混杂和效应修饰所致。在没有令人信服的机制解释流行病学证据的情况下，目前证据还不够有说服力，因此，对心血管疾病报告的统计关联的因果关系解释是不可靠的，但不能排除。炎症过程是辐射可能改变动脉粥样硬化疾病过程的最可能机制。如果通过这种机制，低剂量电离辐射能够改变心血管疾病，那么就不能排除非 DNA 靶向效应的作用。
