Cancer risk after renal transplant in autoimmune disease

自身免疫性疾病肾移植后的癌症风险

• 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
• 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' 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; 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' 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

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）：在过去的三十年中，终末期肾脏疾病（ESRD）的患病率和肾移植的表现显着增加。肾移植的最常见指征包括糖尿病（31％），多囊性肾脏疾病（12％），高血压性肾脏硬化（9％）和全身性狼疮（3％）。尽管移植可改善生存和生活质量，但它与风险增加有关 对于某些癌症，包括淋巴增生性癌症（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，人们认为，至少有一些这种风险是由免疫抑制药物暴露赋予的，但其他假设援引了先前合并症的重要性，甚至可能是先天的免疫系统激活。 文献还突出了几种自身免疫性疾病（包括全身性红斑狼疮（SLE））的癌症风险特征非常相似。这些患者具有过度活跃的免疫系统，会引起受影响组织的炎症和损害。像器官移植患者一样，SLE患者也经常接受免疫抑制治疗的长期治疗。除了药物赋予的癌症风险可能增加外，还有证据表明SLE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 区分这两个因素对自身免疫性疾病（如SLE）的癌症风险的独立影响。 迄今为止，没有人特别研究那些接受肾移植的SLE患者是否与非鲁am移植患者相比，患癌症的风险增加。在当前的试点项目中，我们计划检查美国肾脏数据系统（USRDS）先前收集的数据，以研究肾脏移植患者的癌症风险，无论是超过而全部和通过指示分层（即ESRD是否与SLE与非律师事件有关）。我们的主要目的是研究肾脏移植受者的癌症风险，无论是全部，都通过适应症进行分层（即ESRD是否与SLE相对于非卢比斯原因有关）。该试点项目中要探讨的主要假设是，与具有肾脏移植的非鲁pus迹象的患者相比，SLE患者雷娜移植后的癌症风险最高。在次要分析中，我们还将比较其他重要癌症类型的癌症风险。 USRD中的大量受试者为研究癌症的风险提供了一个独特的机会，以ESRD的原因分层，因此我们可以开始研究因自身免疫性疾病（如SLE）（如SLE）是否患有ESRD患者的问题，例如SLE的癌症风险特别高。 公共卫生相关性：过去三十年来，末期肾脏疾病（ESRD）的肾脏移植有所增加。移植后，某些癌症的风险增加了某些癌症，包括非霍奇金淋巴瘤和肺，皮肤，肝脏和外阴阴道区域的风险。同时，患有慢性自身免疫性疾病的患者，全身性红斑狼疮（SLE），他们面临可能发展为ESRD的肾脏风险和肾脏损害的风险，也有发展类似癌症的风险。目前，人们认为，用于治疗SLE的免疫抑制药物赋予了一些增加的癌症风险，并防止移植后排斥反应。但是，还有其他可能导致癌症风险增加的原因，包括免疫系统的异常。这项初步研究将检查ESRD移植后SLE的患者是否与没有SLE的患者也接受了肾脏移植的患者的风险增加。这项研究将回答一个问题，即患有自身免疫性疾病（例如SLE）的患者是否患有转移后患癌症的风险异常高。