Studies of Populations Exposed to Therapeutic Medical Radiation and Other Agents

REB调查人员使用监测流行病学和最终结果计划癌症登记数据库评估了所有癌症之后发生多种癌症的风险，其中包括1973年至2008年确诊的200多万癌症幸存者。2006年出版的《多原发癌》专著中的有趣发现被用于评估与放射和化疗相关的第二种癌症的风险的个人研究。特别感兴趣的研究包括乳腺癌、霍奇金淋巴瘤、非霍奇金淋巴瘤、视网膜母细胞瘤和儿童癌症的幸存者。2012年，首次公布了与放射治疗相关的第二种癌症的比例估计。良性妇科疾病放射治疗后的癌症-近15,000名妇女中因良性妇科疾病接受放射治疗后的癌症死亡率正在更新，以评估实体肿瘤和白血病的风险。儿童癌症生存者研究-在14,000名儿童癌症5年幸存者的队列中，我们对乳腺癌、甲状腺、唾液腺、骨、软组织和皮肤癌的第二原发癌进行了嵌套病例对照研究，以评估放射和化疗与这些癌症风险的关系。一项新的发现是，在暴露在甲状腺辐射低于20GY的患者中，甲状腺癌的风险与先前使用烷化剂治疗有关。对第二次乳腺癌的新分析与以前的癌症治疗和潜在的效果修饰物有关，已经启动。CCSS也是一种独特的资源和难得的机会，可以用来研究基因-辐射相互作用的潜力。特别值得一提的是，生物检疫剂的可获得性、关于放射和化疗剂量的高质量信息以及暴露在队列中的年轻年龄。我们目前正在对这一队列中的后续肿瘤进行全基因组关联研究(10597)。消化性溃疡患者的癌症风险-正在对2,000名接受辐射的消化性溃疡患者和2,000名未经辐射的消化性溃疡患者进行比较，以完善所有癌症和心脏疾病的剂量相关风险，并模拟这些结果的剂量估计的不确定性。质子和强度调制放射治疗有可能向肿瘤提供最大剂量，同时将可能导致第二次癌症的周围组织的剂量降至最低。SEER-Medicare和当地癌症登记处的可行性工作正在进行中。对接受放射治疗的不同队列中的造血细胞恶性肿瘤进行RF分析-使用各种数学和统计模型对日本原子弹幸存者和接受治疗的群体中与电离辐射暴露相关的癌症风险进行平行分析。终点包括所有血液病癌症，特别是白血病(包括慢性淋巴细胞白血病(CLL))、霍奇金斯病、非霍奇金淋巴瘤(NHL)和多发性骨髓瘤。这些模型考虑了内、外照射(包括近距离放射治疗)导致的细胞重新繁殖和重新分布，以及暴露时年龄和年龄等因素。辐射剂量-反应和第二原发胃肠道癌(胃肠道癌、胰腺癌和食道癌)的国际研究正在霍奇金淋巴瘤、睾丸癌、乳腺癌和宫颈癌的幸存者中进行，以提供关于辐射剂量和随后发生胃肠道癌风险的新数据。到目前为止的研究结果表明，乳腺癌后患食道癌的风险随剂量增加而增加。对HL、睾丸和宫颈癌后胃肠道恶性肿瘤风险的分析以及相关的剂量学方法项目正在进行中。队列联合体中第二癌症的风险因素-正在评估在NCI队列联合体中研究第二癌症的可行性。Kaiser乳腺癌后第二癌症-对侧乳房的病因可能与治疗、遗传和生活方式危险因素有关。我们正在探索在三个不同的队列中研究对侧乳腺癌的治疗和可改变的生活方式危险因素的可行性。视网膜母细胞瘤后的第二种癌症-继续监测1850名视网膜母细胞瘤幸存者队列中所有第二种原发癌症的发病率和死亡率，主要是与过去放疗和化疗有关的骨、软组织和黑色素瘤。关于RB1突变和第二种癌症风险的研究正在进行中。

REB investigators evaluate the risks of multiple cancers following all cancers using the Surveillance Epidemiology and End Results Program cancer registry database including more than 2 million cancer survivors diagnosed from 1973 to 2008. Interesting findings from the 2006 Multiple Primary Monograph have been followed up with individual studies evaluating risk of radiation-related and chemotherapy-related second cancers. Particular studies of interest include of survivors of breast cancer, Hodgkin lymphoma, non-Hodgkin lymphoma, retinoblastoma, and childhood cancers. In 2012 the first estimates of the proportion of second cancers related to radiotherapy were published.Cancer Following Radiotherapy for Benign Gynecologic Disorders - Cancer mortality following radiation treatment for benign gynecologic conditions in a cohort of nearly 15,000 women with individual radiation dose data is being updated to evaluate solid tumor and leukemia risk. Results were submitted for publication in 2012.Childhood Cancer Survivor Study - In a cohort of 14,000 5-year survivors of childhood cancer we performed nested case-control studies of second primary cancers of the breast, thyroid gland, salivary gland, bone, soft tissue and skin to evaluate the relationship between radiation and chemotherapy and risk of these cancers. A novel finding was that thyroid cancer risk was related to prior treatment with alkylating agents among patients exposed to radiation less than 20 Gy to the thyroid. New analyses of second breast cancers in relation to prior cancer treatment and potential effect modifiers has been initiated. The CCSS also is a unique resource and a rare opportunity in which to examine the potential for gene-radiation interaction. Particularly noteworthy are the availability of biospecimens, high quality information on doses of radiation and chemotherapy, and the young age at exposure of the cohort. We are currently performing a genome wide association study of subsequent neoplasms within this cohort (10597).Cancer Risk in Peptic Ulcer Patients - A of cohort of 2000 irradiated peptic ulcer patients is being compared to 2000 non-irradiated peptic ulcer patients to refine the dose-related risk for all cancers and cardiac disease and model the uncertainty in the dose estimates for these outcomes.Proton and intensity-modulated radiation therapy have the potential to deliver maximal doses to the tumor while minimizing dose to the surrounding tissues which may cause second cancers. Feasibility work in SEER-Medicare and local cancer registries is in progress.RF Analysis of Hematopoietic Malignancies in Various Radiotherapeutically Irradiated Cohorts - Parallel analysis using a variety of mathematical and statistical models of cancer risks associated with ionizing radiation exposure in the Japanese atomic bomb survivors and in therapeutically irradiated groups. Endpoints include all hematologic cancers, specifically leukemia (including chronic lymphocytc leukemia (CLL)), Hodgkins disease, non-Hodgkins lymphoma (NHL), and multiple myeloma. The models take account of cell repopulation and redistribution as a result of internal and external radiation exposure (including brachytherapy), and also factors such as age at exposure and attained age.Radiation Dose-Response and Second Primary Cancers of Stomach, Esophagus, and Pancreas - An international study of second primary gastrointestinal (GI stomach cancer, pancreatic cancer, and esophageal cancer) cancers is being conducted among survivors of Hodgkin lymphoma testis cancer, breast and cervical cancer to provide new data on radiation dose and subsequent risk of GI cancer. Findings to date have demonstrated a dose-related increased risk of esophageal cancer following breast cancer. Analyses of GI malignancy risk after HL and testis and cervical cancers as well as related dosimetry methods projects are in progress.Risk Factors for Second Cancers in the Cohort Consortium - The feasibility of studying second cancers in the NCI Cohort Consortium is being assessed.Second Cancers after Breast Cancer in Kaiser - The etiology of contralateral breast is probably related to treatment, genetic and lifestyle risk factors. We are exploring the feasibility of studying treatment and modifiable lifestyle risk factors for contralateral breast cancer in three different cohorts. Second Cancers Following Retinoblastoma - A cohort of 1,850 Retinoblastoma survivors continues to be monitored for the incidence and mortality of all second primary cancers, primarily of the bone, soft tissue, and melanoma in relation to past radiotherapy and chemotherapy. Studies of RB1 mutations and second cancer risks are in progress.