寿命研究(LSS)中对所有实体癌发病率(1958-2009)的最新分析显示,男性而非女性的辐射剂量反应曲率上升。在0-2Gy剂量范围内,还观察到所有实体癌死亡率(1950-2003年)的性别平均相对相对风险(ERR)的上升曲率。由于LSS中非线性的原因尚未完全理解,我们使用类似的方法对所有实体癌死亡率和发病率进行了剂量反应分析[1958-2009年随访,DS02R1剂量,包括轰炸时的非城市受试者(NIC)]和统计模型。从广岛和长崎癌症登记处确定了癌症事件,而死因是根据日本各地的死亡证明确定的。该研究包括105,444名LSS受试者,他们在1958年1月1日之前还活着并且不知道患有癌症(80,205名剂量估计和25,239名NIC受试者)。在1958年至2009年之间,有310万人年(PY)和22,538个实体癌的发病率分析和380万PY和15,419个实体癌死亡的死亡率分析。我们将针对吸烟进行调整的性别特异性ERR模型拟合到两种类型的数据。在整个剂量范围内,实体癌死亡率剂量-反应在男性中表现出边缘显著向上曲率(P=0.062),在女性中表现出显著向上曲率(P=0.010);对于实体癌发病率,和以前一样,我们发现男性(P=0.001)有显著的上升曲率,而女性(P=0.624)则没有。剂量反应曲率大小的性别差异对癌症发病率有统计学意义(P=0.017),但对癌症死亡率无统计学意义(P=0.781)。在0-2Gy范围和有限的低剂量范围内的分析结果通常支持对每种结果的整个剂量范围内的性别特异性剂量反应形状的推论。按日历周期划分的性别曲率模式(1958-1987年与1988-2009)和暴露年龄(0-19岁vs.20-83)在死亡率和发病率数据之间有所不同,尤其是女性,尽管对于每个结局,在两个日历期的0-19岁男性幸存者中以及在最近一期的0-19岁女性幸存者中都有弯曲的迹象。总的来说,我们的研究结果表明,LSS中所有实体癌剂量反应的向上曲率既不是男性特有的,也不是发病率数据特有的;其证据似乎取决于所有实体癌组的部位组成以及暴露时或暴露时的年龄.对癌症死亡率和发病率的进一步随访和特定部位分析对于确认年轻幸存者剂量反应曲率的新趋势并揭示影响因素和部位将是重要的。
Recent analysis of all solid cancer incidence (1958-2009) in the Life Span Study (LSS) revealed evidence of upward curvature in the radiation dose response among males but not females. Upward curvature in sex-averaged excess relative risk (ERR) for all solid cancer mortality (1950-2003) was also observed in the 0-2 Gy dose range. As reasons for non-linearity in the LSS are not completely understood, we conducted dose-response analyses for all solid cancer mortality and incidence applying similar methods [1958-2009 follow-up, DS02R1 doses, including subjects not-in-city (NIC) at the time of the bombing] and statistical models. Incident cancers were ascertained from Hiroshima and Nagasaki cancer registries, while cause of death was ascertained from death certificates throughout Japan. The study included 105,444 LSS subjects who were alive and not known to have cancer before January 1, 1958 (80,205 with dose estimates and 25,239 NIC subjects). Between 1958 and 2009, there were 3.1 million person-years (PY) and 22,538 solid cancers for incidence analysis and 3.8 million PY and 15,419 solid cancer deaths for mortality analysis. We fitted sex-specific ERR models adjusted for smoking to both types of data. Over the entire range of doses, solid cancer mortality dose-response exhibited a borderline significant upward curvature among males (P = 0.062) and significant upward curvature among females (P = 0.010); for solid cancer incidence, as before, we found a significant upward curvature among males (P = 0.001) but not among females (P = 0.624). The sex difference in magnitude of dose-response curvature was statistically significant for cancer incidence (P = 0.017) but not for cancer mortality (P = 0.781). The results of analyses in the 0-2 Gy range and restricted lower dose ranges generally supported inferences made about the sex-specific dose-response shape over the entire range of doses for each outcome. Patterns of sex-specific curvature by calendar period (1958-1987 vs. 1988-2009) and age at exposure (0-19 vs. 20-83) varied between mortality and incidence data, particularly among females, although for each outcome there was an indication of curvature among 0-19-year-old male survivors in both calendar periods and among 0-19-year-old female survivors in the recent period. Collectively, our findings indicate that the upward curvature in all solid cancer dose response in the LSS is neither specific to males nor to incidence data; its evidence appears to depend on the composition of sites comprising all solid cancer group and age at exposure or time. Further follow up and site-specific analyses of cancer mortality and incidence will be important to confirm the emerging trend in dose-response curvature among young survivors and unveil the contributing factors and sites.