Studies of Populations Exposed to Therapeutic Medical Radiation and Other Agents

REB研究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所有癌症后多种癌症的风险，该数据库包括1973年至2008年诊断的200多万癌症幸存者。2006年《多重原发专论》的有趣发现被用于评估放射相关和化疗相关的二次癌症风险的个别研究。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年公布了与放疗相关的第二次癌症比例的首次估计。良性妇科疾病放射治疗后的癌症-在近15,000名妇女中进行的良性妇科疾病放射治疗后的癌症死亡率，个人放射剂量数据正在更新，以评估实体瘤和白血病的风险。结果于2012年提交发表。儿童癌症幸存者研究——在14000名5年儿童癌症幸存者的队列中，我们对乳腺癌、甲状腺、唾液腺、骨、软组织和皮肤的第二原发性癌症进行了巢式病例对照研究，以评估放疗和化疗与这些癌症风险之间的关系。一项新的发现是甲状腺癌风险与先前接受烷基化剂治疗的患者暴露于低于20 Gy的甲状腺辐射有关。新的分析第二乳腺癌与既往癌症治疗和潜在效果调节剂的关系已经开始。CCSS也是研究基因-辐射相互作用潜力的独特资源和难得机会。特别值得注意的是生物标本的可获得性、关于放射和化疗剂量的高质量信息以及受照射队列的年龄小。目前，我们正在对该队列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——对2000名接受过放射治疗的消化性溃疡患者与2000名未接受放射治疗的消化性溃疡患者进行了一项队列研究，以完善所有癌症和心脏病的剂量相关风险，并对这些结果的剂量估计的不确定性进行建模。质子和调强放射治疗有可能向肿瘤提供最大剂量，同时将可能引起第二种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。各种放疗人群中造血恶性肿瘤的射频分析-在日本原子弹幸存者和治疗放疗组中使用与电离辐射暴露相关的癌症风险的各种数学和统计模型进行平行分析。终点包括所有血液学癌症，特别是白血病（包括慢性淋巴细胞白血病（CLL））、霍奇金病、非霍奇金淋巴瘤（NHL）和多发性骨髓瘤。这些模型考虑了内部和外部辐射照射（包括近距离放射治疗）导致的细胞再生和再分布，以及暴露年龄和达到年龄等因素。辐射剂量-反应和胃癌、食道癌和胰腺癌的第二原发性胃肠道（胃肠道胃癌、胰腺癌和食道癌）癌症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，以提供有关辐射剂量和胃肠道癌后续风险的新数据。迄今为止的研究结果表明，乳腺癌后食道癌的风险增加与剂量有关。HL、睾丸癌和宫颈癌后胃肠道恶性肿瘤风险分析及相关剂量学方法项目正在进行中。队列联盟中第二种癌症的危险因素-正在评估在NCI队列联盟中研究第二种癌症的可行性。对侧乳腺癌的病因可能与治疗、遗传和生活方式风险因素有关。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——一组1,850名视网膜母细胞瘤幸存者继续监测所有第二原发癌症的发病率和死亡率，主要是骨、软组织和黑色素瘤，与过去的放疗和化疗有关。有关RB1突变和二次癌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.