Late Effects in Wilms Tumor Survivors and Offspring

对肾母细胞瘤幸存者和后代的迟发影响

• 批准号: 7015076
• 负责人: NORMAN E BRESLOW
• 金额: $ 93.04万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-08-15 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7015076
• 关键词: Wilms' tumor; cancer complication; clinical research; congestive heart failure; family; human mortality; human subject; longitudinal human study; pregnancy disorder; renal failure; respiratory insufficiency /failure

DESCRIPTION (provided by applicant): This proposal is to continue the follow-up of children and young adults who were successfully treated for Wilms tumor on protocol studies of the National Wilms Tumor Study Group (NWTSG), as well as their offspring. With current therapy, 90 percent of children treated for Wilms tumor will be cured of their disease. However, survivors are at risk for delayed complications of their disease and treatment that can compromise the quality and duration of that survival. Therapy for Wilms tumor has changed over time but still includes surgery, multi-agent chemotherapy, and (for some) radiation therapy. As children are treated for Wilms tumor in early childhood, it has taken many years of follow-up to appreciate some of these long- term effects. For some, we are just beginning to better define these effects 10-20 years post treatment, The mechanisms underlying many of these long term-complications remain unknown, and thus preventive strategies have yet to be established. In addition, as we unravel the complex genetic heterogeneity surrounding the etiology and pathogenesis of Wilms tumor, this may provide important clues to the mechanisms underling long-term complications. With respect to late effects, we will determine the incidence, spectrum and mechanisms of disease, treatment and host-related risk factors for selected life-threatening chronic toxicities in Wilms tumor patients. These include a) congestive heart failure b) respiratory failure c) renal failure and d) second malignant neoplasms (SMN). Related to this, we will determine the incidence and cause of late mortality in Wilms tumor patients and compare with age and sex-specific national population rates. Reproductive epidemiology will be studied with respect to natality, pregnancy outcomes and complications, and congenital or hereditary diseases in the offspring. By using established family history data and pedigrees and following offspring of survivors, heritability and recurrence risks will be estimated and clinical heterogeneity will be explored. We will collaborate with molecular biologists by facilitating access to particularly informative subgroups of Wilms tumor patients.

描述（申请人提供）：本提案将继续跟进 成功治疗肾母细胞瘤的儿童和年轻人 国家肾母细胞瘤研究组 (NWTSG) 的方案研究，以及 他们的后代。根据目前的治疗方法，90% 的儿童都接受了肾母细胞瘤治疗 肿瘤将治愈他们的疾病。然而，幸存者面临着以下风险： 疾病和治疗的延迟并发症可能会损害患者的健康 生存的质量和持续时间。肾母细胞瘤的治疗方法已经改变 时间，但仍包括手术、多药化疗，以及（对于某些人） 放射治疗。由于儿童在幼儿期接受肾母细胞瘤治疗， 经过多年的跟踪，我们才认识到其中一些长期的 影响。对于某些人来说，我们才刚刚开始更好地定义这些影响 10-20 治疗后数年，许多这些长期的机制 术语并发症仍然未知，因此预防策略尚未制定 被成立。此外，当我们揭示复杂的遗传异质性时 围绕肾母细胞瘤的病因和发病机制，这可能提供 长期并发症发生机制的重要线索。和 关于后期影响，我们将确定发生率、频谱和 选定的疾病机制、治疗和宿主相关危险因素 肾母细胞瘤患者中危及生命的慢性毒性。这些包括： 充血性心力衰竭 b) 呼吸衰竭 c) 肾衰竭 d) 第二 恶性肿瘤（SMN）。与此相关，我们将确定发病率和 肾母细胞瘤患者晚期死亡的原因以及与年龄和年龄的比较 特定性别的全国人口比率。生殖流行病学将 研究了出生率、妊娠结局和并发症，以及 后代患有先天性或遗传性疾病。通过利用已建立的家庭 历史数据和谱系以及幸存者的后代、遗传力 评估复发风险并评估临床异质性 探索过。我们将与分子生物学家合作，促进访问 向维尔姆斯肿瘤患者的特别信息亚组提供信息。