MicroRNA Related Genetic Variation in Bladder Cancer Recurrence and Survival

膀胱癌复发和生存中 MicroRNA 相关的遗传变异

• 批准号: 8620626
• 负责人: Brock Clarke Christensen
• 金额: $ 20.51万
• 依托单位: DARTMOUTH COLLEGE
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-04-01 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8620626
• 关键词: 3' Untranslated Regions; Accounting; Binding; Biogenesis; Bioinformatics; Biological; Biological Markers; Bladder Neoplasm; Cancer Patient; Cancer Prognosis; Carcinoma; Case-Control Studies; Cataloging; Catalogs; Cessation of life; Cleaved cell; Clinical; Clinical Management; Cystoscopy; Development; Diagnosis; Disease; Epidemiologic Studies; Epidemiology; Expenditure; Functional RNA; General Population; Genes; Genetic; Genetic Markers; Genetic Translation; Genetic Variation; Genotype; Human; Individual; KRAS2 gene; Life; Literature; Malignant Neoplasms; Malignant neoplasm of pharynx; Malignant neoplasm of urinary bladder; Messenger RNA; MicroRNAs; Molecular; Morbidity - disease rate; Muscle; Oligonucleotides; Outcome; Parents; Patients; Play; Population Study; Process; Processed Genes; Protocols documentation; Recurrence; Regulation; Resources; Risk; Role; Single Nucleotide Polymorphism; Site; Specimen; Testing; Training; Transcript; Urothelial Cell; Variant; Visit; Work; base; cancer recurrence; case-based; clinical decision-making; cost; follow-up; genetic variant; genome wide association study; genome-wide; insight; malignant mouth neoplasm; mortality; novel; outcome forecast; population based; prognostic; public health relevance; screening; success; tool; tumor; tumorigenesis

DESCRIPTION (provided by applicant): MicroRNA related genetic variation and bladder cancer recurrence and survival Over 500,000 individuals in the U.S. are living with a diagnosis of bladder cancer, a disease where over half of cases will recur. With a high likelihood of recurrence, the clinical management of bladder cancer includes routine screening of patients with invasive cystoscopy, resulting in significant patient morbidity. Further, in part because invasive cystoscopy is repeated over the course of disease, bladder cancer is the most expensive cancer to treat per capita, accounting for nearly 3.7 billion U.S. dollars (2001 dollars) in annual expenditures. Currently there is a lack of clinically used determinants that can inform on the risk of recurrence and survival. Here, we propose to systematically investigate a novel class of genetic variation - microRNA-related genetic variation (miR-SNPs) - for new determinants of bladder cancer recurrence and survival. MiR-SNPs include variation in miRNA target sites on mRNA transcripts, SNPs in miRNA genes, and SNPs in genes that participate in miRNA biogenesis and processing. While GWAS approaches have had some success, miR- SNPs have not been well represented on GWAS panels, and there is a very limited understanding of miRNA- related natural genetic variation. Almost exclusively non-coding, miR-SNPs clearly have critical regulatory capacity and the rapidly emerging literature has begun to demonstrate associations between candidate miR- SNPs and both risk and prognosis of human cancers, though there is a gap in the study of bladder cancers. Recent and continued advances in miRNA target site prediction allows a more comprehensive cataloging and characterization of miR-SNPs that can be used for hypothesis testing in population studies. The primary aim of this work is to use proven epidemiologic resources to identify miR-SNPs associated with recurrence and survival of bladder cancer. Our group has completed a geographically defined, population-based epidemiologic study of bladder cancer that includes a comprehensive assessment of patient recurrences and survival. To our knowledge this is the only study of its kind in the U.S., and one of the few worldwide from which inferences of the general population can be made regarding the determinant of bladder cancer prognosis. Our approach will extend well beyond candidate miR-SNP approaches by genotyping over 18,000 miR-SNPs. We propose to identify a new class of genetic markers of bladder cancer recurrence and survival that will contribute to the development of clinical decision-making tools to stratify patients into follow-up groups based on their likelihood of recurrence. In this way we aim to maximize the impact and translational potential of our identified markers, reduce patient morbidity and mortality, and decrease the cost burden of routine cystoscopy by shifting the current paradigm of bladder cancer management.

描述（由申请人提供）：MicroRNA相关遗传变异与膀胱癌复发和生存在美国有超过50万人被诊断患有膀胱癌，其中超过一半的病例会复发。膀胱癌复发的可能性很大，临床对膀胱癌患者进行常规有创膀胱镜检查，导致患者的发病率很高。此外，部分原因是侵入性膀胱镜检查在病程中反复进行，膀胱癌是人均治疗费用最高的癌症，占近37亿美元（2001年美元）。