Cancer risk after renal transplant in autoimmune disease

自身免疫性疾病肾移植后的癌症风险

基本信息

批准号：
8387402
负责人：
Rosalind Ramsey-Goldman
金额：
$ 9.19万
依托单位：
NORTHWESTERN UNIVERSITY AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-07-06 至 2014-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8387402
关键词：
Accounting Affect Area Autoimmune Diseases Autoimmune Process Chronic Clinical Collaborations Comorbidity Complex Country Data Data Sources Databases Diabetes Mellitus Disease Drug Exposure Drug usage End stage renal failure Ethnic Origin Etiology Funding Future Genetic Graft Survival High-Risk Cancer Immune system Immunosuppressive Agents Inflammation Information Systems Kidney Kidney Failure Kidney Transplantation Lead Life Light Link Literature Liver Lung Neoplasms Lupus Lupus Nephritis Malignant Neoplasms Malignant neoplasm of liver Malignant neoplasm of lung Nephritis Nephrosclerosis Non-Hodgkin&apos s Lymphoma Organ Organ Transplantation Patients Performance Pharmaceutical Preparations Pilot Projects Polycystic Kidney Diseases Prevalence Quality of life Race Research Rheumatism Risk Series Serological Skin Skin Cancer Source Staging Systemic Lupus Erythematosus Therapeutic immunosuppression Time Tissues Transplant Recipients Transplantation Tumor Suppressor Genes United States Variant Work adverse outcome cancer risk cancer type carcinogenesis high risk improved middle age prevent

项目摘要

DESCRIPTION (provided by applicant): The prevalence of end-stage renal disease (ESRD) and the performance of renal transplantation have risen dramatically in the past three decades. The most common indications for renal transplantation include diabetes (31%), polycystic kidney disease (12%), hypertensive nephrosclerosis (9%) and systemic lupus (3%). Although transplantation improves both survival and quality of life, it is associated with an increased risk for certain cancers including lymphoproliferative cancers (especially non-Hodgkin lymphoma, NL), lung cancer, skin cancer, liver cancer, and vulvovaginal cancers. It is currently believed that at least some of this risk is conferred by immunosuppressive drug exposures, but other hypotheses have invoked the importance of prior co-morbidity, and perhaps even innate immune system activation. The literature also highlights a very similar cancer risk profile in several autoimmune rheumatic diseases, including systemic lupus erythematosus (SLE). These patients have an overactive immune system that causes inflammation and damage in affected tissue. Like organ transplant patients, SLE patients often also undergo long-term treatment with immunosuppressive therapy. In addition to possible increased risk for cancer conferred by medications, there is evidence that SLE disease activity itself is associated with increased risk of certain malignancies. Due to correlations between drugs and disease activity, it is difficult to differentiate the independent effects of these two factors, on cancer risk in autoimmune diseases like SLE. To date, no one has specifically examined whether those patients with SLE who undergo renal transplantation have an increased risk of cancer compared to non-lupus transplant patients. In the current pilot project, we plan to examine previously collected data in the United States Renal Data System (USRDS) to study cancer risk in renal transplant patients, both over-all, and stratified by indication (that is, whether ESRD is related to SLE versus non-lupus causes). Our primary aims are to study cancer risk in renal transplant recipients, both over-all, and stratified by indication (i.e. whether ESRD is related to SLE versus non-lupus causes). The primary hypothesis to be explored in this pilot project is that cancer risk after rena transplantation is highest in SLE patients, compared to patients with non-lupus indications for renal transplantation. We will additionally compare cancer risk for other important cancer types, in secondary analyses. The enormous pool of subjects in the USRDS affords a unique opportunity to study cancer risk stratified by reason for ESRD, so that we can begin to examine the question of whether patients with ESRD due to autoimmune diseases like SLE have a particularly high risk of cancer, post-transplantation. PUBLIC HEALTH RELEVANCE: Renal transplantation for end stage renal disease (ESRD) has increased during the last thirty years. An increased risk of certain cancers including non-Hodgkin's Lymphoma and tumors of the lung, skin, liver, and vulvovaginal areas following transplantation has noted. At the same time, patients with a chronic autoimmune disorder, systemic lupus erythematosus (SLE), who are at risk for inflammation and damage to their kidneys which can progress to ESRD, are also at risk for developing similar cancers. It is currently believed that some of the increased risk of cancer is conferred by immunosuppressive drugs used to treat SLE and prevent rejection following transplantation. However, there are other possible causes of the increased risk of cancer including abnormalities of the immune system. This pilot study will examine whether patients with SLE following transplantation for ESRD are at increased risk of cancer compared to patient without SLE who also had a renal transplant. This study will answer the question as to whether patients with an autoimmune disorder such as SLE have an unusually high risk of developing cancer post-transplantation.

描述（由申请人提供）：在过去三十年中，终末期肾病（ESRD）的患病率和肾移植的表现急剧上升。肾移植最常见的适应症包括糖尿病（31%）、多囊肾病（12%）、高血压肾硬化（9%）和系统性狼疮（3%）。尽管移植可以提高生存率和生活质量，但也会增加风险适用于某些癌症，包括淋巴增殖性癌症（尤其是非霍奇金淋巴瘤，NL）、肺癌、皮肤癌、肝癌和外阴阴道癌。目前认为，至少部分风险是由免疫抑制药物暴露造成的，但其他假设也提到了先前合并症的重要性，甚至可能是先天免疫系统激活的重要性。文献还强调了几种自身免疫性风湿病（包括系统性红斑狼疮（SLE））中非常相似的癌症风险特征。这些患者的免疫系统过度活跃，会导致受影响的组织发炎和损伤。与器官移植患者一样，系统性红斑狼疮患者也经常接受长期的免疫抑制治疗。除了药物可能增加患癌症的风险外，有证据表明 SLE 疾病活动本身与某些恶性肿瘤的风险增加有关。由于药物与疾病活动之间的相关性，很难区分这两个因素对系统性红斑狼疮等自身免疫性疾病癌症风险的独立影响。迄今为止，没有人专门研究那些接受肾移植的 SLE 患者与非狼疮移植患者相比，患癌症的风险是否增加。在当前的试点项目中，我们计划检查之前在美国肾脏数据系统（USRDS）中收集的数据，以研究肾移植患者的癌症风险，包括总体风险和按适应症分层（即 ESRD 是否与SLE 与非狼疮原因）。我们的主要目标是研究肾移植受者的癌症风险，包括总体风险和按适应症分层的风险（即 ESRD 是否与 SLE 相关，与非狼疮原因相关）。该试点项目要探讨的主要假设是，与具有肾移植非狼疮指征的患者相比，SLE 患者肾移植后的癌症风险最高。我们还将在二次分析中比较其他重要癌症类型的癌症风险。 USRDS 中庞大的受试者库提供了一个独特的机会来研究按 ESRD 原因分层的癌症风险，以便我们可以开始研究因自身免疫性疾病（如 SLE）而导致 ESRD 患者是否具有特别高的癌症风险的问题。移植后。公众健康相关性：过去三十年来，用于治疗终末期肾病 (ESRD) 的肾移植有所增加。移植后患某些癌症的风险增加，包括非霍奇金淋巴瘤以及肺、皮肤、肝癌和外阴阴道区域的肿瘤。与此同时，患有慢性自身免疫性疾病系统性红斑狼疮 (SLE) 的患者也有患类似癌症的风险，这些患者的肾脏有炎症和损伤，可能会进展为 ESRD。目前认为，用于治疗系统性红斑狼疮和预防移植后排斥反应的免疫抑制药物会增加患癌症的风险。然而，还有其他可能导致癌症风险增加的原因，包括免疫系统异常。这项试点研究将检查因终末期肾病（ESRD）移植后患有系统性红斑狼疮（SLE）的患者与接受肾移植但没有系统性红斑狼疮（SLE）的患者相比，患癌症的风险是否增加。这项研究将回答这样的问题：患有系统性红斑狼疮等自身免疫性疾病的患者在移植后患癌症的风险是否异常高。