Tokarskaya Z B, Scott B R, Zhuntova G V, Okladnikova N D, Belyaeva Z D, Khokhryakov V F, Schöllnberger H, Vasilenko E K
Southern Ural Biophysics Institute, Ozyorsk, Russia.
Health Phys. 2002 Dec;83(6):833-46. doi: 10.1097/00004032-200212000-00011.
For radiation-related cancer risk evaluation, it is important to assess not only influences of individual risk factors but also their interactive effects (e.g., additive, multiplicative, etc.). Multivariate analysis methods adapted for interactive effects allow such assessments. We have used a multivariate analysis approach to investigate the pair-wise interactions of the previously identified three main etiological factors for lung cancer induction in Russian workers of the Mayak Production Association (PA) nuclear enterprise. These three factors are as follows: (1) body burden of inhaled plutonium-239 (239Pu), an influence on absorbed alpha-radiation dose; (2) cumulative, absorbed external gamma-radiation dose to the lung; and (3) level of cigarette smoking as indicated by a smoking index (SI). The SI represents the cigarettes smoked per day times years smoking. The Mayak PA workers were exposed by inhalation to both soluble and insoluble forms of 239Pu. Based on a cohort of 4,390 persons (77% male), we conducted a nested, case-control study of lung cancer induction using 486 matched cases and controls. Each case was matched to two controls. Matching was based on five factors: sex, year of birth, year work began, profession, and workplace. Three levels of smoking were considered: low (SI = 1 to 499), used as a reference level; middle (SI = 500 to 900); and high (SI = 901 to 2,000). For lung cancer induction, a supra-multiplicative effect was demonstrated for high external gamma-ray doses (> 2.0 Gy) plus high 239Pu intakes (body burden >2.3 kBq). This observation is consistent with the hypothesis of curvilinear dose-response relationships for lung cancer induction by high- and low-LET radiations. The interaction between radiation (external gamma rays or 239Pu body burden) and cigarette smoke was found to depend on the smoking level. For the middle level of smoking in combination with gamma radiation (> 2.0 Gy) or 239Pu body burden (> 2.3 kBq), results were consistent with additive effects. However, for the high level of smoking in combination with gamma radiation (> 2.0 Gy) or 239Pu body burden (> 2.3 kBq), results were consistent with the occurrence of multiplicative effects. These results indicate that low-dose risk estimates for radiation-induced lung cancer derived without adjusting for the influence of cigarette smoking could be greatly overestimated. Further, such systematic error may considerably distort the shape of the risk vs. dose curve and could possibly obscure the presence of a dose threshold for radiation-induced lung cancer.
对于辐射相关癌症风险评估而言，不仅要评估个体风险因素的影响，还要评估它们的交互作用（例如相加、相乘等），这一点很重要。适用于交互作用的多变量分析方法能够进行此类评估。我们采用多变量分析方法，研究了马亚克生产协会（PA）核企业俄罗斯工人中先前确定的肺癌诱发三大主要病因因素的两两交互作用。这三个因素如下：（1）吸入钚 - 239（239Pu）的体内负荷，其对吸收的α辐射剂量有影响；（2）肺部累积吸收的外照射γ辐射剂量；（3）吸烟指数（SI）所表明的吸烟水平。吸烟指数表示每天吸烟支数乘以吸烟年数。马亚克PA工人通过吸入接触了可溶性和不可溶性两种形式的239Pu。基于4390人的队列（77%为男性），我们使用486例匹配的病例和对照进行了肺癌诱发的巢式病例对照研究。每个病例与两个对照匹配。匹配基于五个因素：性别、出生年份、开始工作年份、职业和工作场所。考虑了三个吸烟水平：低水平（SI = 1至499），用作参考水平；中等水平（SI = 500至900）；高水平（SI = 901至2000）。对于肺癌诱发，高外照射γ射线剂量（> 2.0 Gy）加上高239Pu摄入量（体内负荷> 2.3 kBq）显示出超相乘效应。这一观察结果与高LET和低LET辐射诱发肺癌的曲线剂量反应关系假说一致。发现辐射（外照射γ射线或239Pu体内负荷）与香烟烟雾之间的相互作用取决于吸烟水平。对于中等吸烟水平与γ辐射（> 2.0 Gy）或239Pu体内负荷（> 2.3 kBq）的组合，结果与相加效应一致。然而，对于高吸烟水平与γ辐射（> 2.0 Gy）或239Pu体内负荷（> 2.3 kBq）的组合，结果与相乘效应的发生一致。这些结果表明，在未调整吸烟影响的情况下得出的辐射诱发肺癌低剂量风险估计可能被大大高估。此外，这种系统误差可能会严重扭曲风险与剂量曲线的形状，并可能掩盖辐射诱发肺癌剂量阈值的存在。
