Studies of Atomic Bomb Survivors

目前正在与辐射效应研究基金会合作，对广岛和长崎原子弹爆炸的94,000名幸存者进行寿命研究。采用队列研究量化环境辐射剂量反应及其与肿瘤组织学亚型、照射年龄、性别、观察年龄、照射后时间等因素的依赖关系。在原子弹爆炸半个多世纪后，从统计数据来看，癌症的风险仍然明显过高。最新的LSS实体癌发病率报告包括LSS幸存者中17,448例第一原发性癌症，其中853例估计是可归因于辐射暴露的超额病例。实体癌作为一个群体和许多个别癌症部位的剂量反应的形状仍然可以用线性模型很好地描述。最重要的发现是，在所有年龄段中，实体癌的超额绝对发病率都在增加。膀胱癌，乳腺癌和肺癌等与辐射暴露相关的过度相对风险很高，而胃癌，乳腺癌，结肠癌和肺癌的过度绝对风险很高。在子宫内和儿童早期接触的人患实体癌的风险尤其高。然而，与辐射相关的癌症风险的时间模式仍然存在不确定性，特别是在原子弹爆炸时年龄小于20岁的幸存者中，需要继续对这一队列进行随访以澄清这一不确定性。一些新发现包括与辐射有关的男性乳腺癌风险过高。甲状腺乳头状微癌，辐射和丙型肝炎感染对肝癌风险的协同相互作用，辐射和吸烟对肺癌风险的加性/倍增效应，以及紫外线和电离辐射暴露对基底细胞皮肤癌的加性效应。目前正在采用多学科的个案方法研究与辐射有关的乳腺癌和卵巢癌的遗传易感性。此前有报道称，早发性乳腺癌（35岁之前）的剂量特异性相对风险极高，这表明遗传易感人群对辐射的敏感性增加。在本研究中，我们比较了早发性和晚发性乳腺癌病例，并利用存档组织研究了BRCA 1/2和其他乳腺癌通路的候选基因。

The Life Span Study (LSS) cohort of 94,000 survivors of the Hiroshima and Nagasaki atomic bombings is being studied in collaboration with the Radiation Effects Research Foundation (RERF). Cohort studies are used to quantify environmental radiation dose response and its dependence on histological subtype of tumor, age at exposure, sex, age at observation, time following exposure and other factors. More than half a century after the atomic bombings, a statistically significant excess risk of cancer is still apparent. The latest LSS solid cancer incidence report includes 17,448 first primary cancers among the LSS survivors, of which 853 are estimated to be excess cases attributable to radiation exposure. The shape of the dose response for solid cancers as a group and for many individual cancer sites continues to be well described by a linear model. The most important finding is that the excess absolute rates for solid cancer increase throughout life for all ages. The excess relative risks associated with radiation exposure are high for cancers of the bladder cancer, breast cancer and lung cancer, whereas excess absolute rates are high for stomach cancer, breast cancer, colon cancer and lung cancer. Solid cancer risks are especially high among these exposed in utero and early childhood. However, the uncertainty remains regarding the temporal patterns of the radiation-related cancer risk, especially among the survivor younger than 20 years of age at the time of the atomic bombings, and continued follow-up of this cohort is needed to clarify this uncertainty. Among several new findings are the radiation-related excess risk of male breast cancer. Thyroid papillary microcarcinoma, a synergistic interaction between radiation and hepatitis C infection on liver cancer risk, an additive/multiplicative effects of radiation and smoking on lung cancer risk, and also an additive effect of ultraviolet and ionizing radiation exposures on basal cell skin cancer. A multidisciplinary case-case approach is in progress to study genetic susceptibility to radiation-related breast cancer and ovarian cancer. This follows the previously reported phenomenon of extremely high, dose-specific relative risks for early-onset breast cancer (before age 35), which suggests increased sensitivity to radiation among a genetically predisposed population subgroup. In this study, early and late-onset breast cancer cases are compared and BRCA 1/2 and other candidate genes in breast cancer pathways are investigated using archived tissues.