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（由申请人提供）：该提案将继续进行后续 成功治疗Wilms肿瘤的儿童和年轻人 国家威尔姆斯肿瘤研究小组（NWTSG）的协议研究以及 他们的后代。使用当前的疗法，有90％接受Wilms治疗的儿童 肿瘤将治愈其疾病。但是，幸存者有风险 其疾病的延迟并发症和治疗可能损害 该生存的质量和持续时间。威尔姆斯肿瘤的治疗已经改变 时间，但仍包括手术，多药化疗，以及（对于某些） 放射治疗。由于儿童在幼儿时接受了威尔姆斯肿瘤的治疗， 欣赏其中一些长期的后续行动花了很多年 效果。对于某些人来说，我们才刚刚开始更好地定义这些效果10-20 治疗后的几年，其中许多漫长的机制 术语符合条件仍然未知，因此预防策略尚未 建立。另外，随着我​​们揭示复杂的遗传异质性 围绕威尔姆斯肿瘤的病因和发病机理，这可能提供 长期并发症基础机制的重要线索。和 尊重晚期效应，我们将确定发生率，频谱和 选定的疾病，治疗和与宿主有关的风险因素的机制 威尔姆斯肿瘤患者中威胁生命的慢性毒性。这些包括a） 充血性心力衰竭b）呼吸衰竭c）肾衰竭，d）第二 恶性肿瘤（SMN）。与此相关的是，我们将确定发生率和 威尔姆斯肿瘤患者死亡晚期的原因，并与年龄和年龄相比 性别特定的全国人口率。生殖流行病学将是 研究了出生，妊娠结局和并发症，以及 后代的先天或遗传性疾病。通过使用已建立的家庭 历史数据和谱系以及追随幸存者的后代，遗传力 并将估算复发风险，临床异质性将是 探索。我们将通过促进访问来与分子生物学家合作 特别是Wilms肿瘤患者的信息亚组。