Hof, J.P., Vermeulen, S.H., van der Heijden, A.G. et al. (8 more authors) (2023) An association study of germline variants in bladder cancer-related genes with the prognosis of on-Muscle Invasive Bladder Cancer. Bladder Cancer, 9 (1). pp. 59-71. ISSN 2352-3727
Abstract
BACKGROUND: Various germline genetic variants are associated with the prognosis of non-muscle invasive bladder cancer (NMIBC). Germline variants in genes frequently somatically mutated in bladder cancer have not been studied thoroughly in relation to risk of recurrence or progression in NMIBC.
OBJECTIVE: To identify germline DNA variants in bladder carcinogenesis-related genes associated with recurrence or progression in NMIBC.
METHODS: We analysed associations between single-nucleotide polymorphisms (SNPs) and NMIBC recurrence and progression using data from the Nijmegen Bladder Cancer Study (NBCS, 1,443 patients). We included 5,053 SNPs within 46 genes known to have mutation, overexpression or amplification in bladder cancer. We included all recurrences in the statistical analysis and performed both single variant analysis and gene-based analysis. SNPs and genes that showed significant or suggestive association (false discovery rate P value < 20%) were followed-up in independent cohorts for replication analysis, through eQTL analysis and tests for association of tumour expression levels with NMIBC recurrence and progression.
RESULTS: Single variant analysis showed no statistically significant associations with recurrence or progression. In gene-based analysis, the aggregate effect of the 25 SNPs in the Cyclin D1 gene (CCND1) was statistically significantly associated with NMIBC recurrence (Punadj = 0.001, PFDR = 0.046), but not with progression (Punadj = 0.17, PFDR = 0.54). Validation analysis in independent cohorts did not confirm the association of CCND1 with NMIBC recurrence.
CONCLUSIONS: We could not identify reproducible associations between common germline variants in bladder carcinogenesis-related genes and NMIBC recurrence or progression.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2023– The authors. Published by IOS Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0 - https://creativecommons.org/licenses/by/4.0/) |
Keywords: | Bladder cancer; candidate gene analysis; genetic association study; progression; recurrence |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > Department of Psychology (Sheffield) The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Medicine and Population Health |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 23 Sep 2024 11:22 |
Last Modified: | 23 Sep 2024 11:22 |
Published Version: | https://content.iospress.com/articles/bladder-canc... |
Status: | Published |
Publisher: | IOS Press |
Refereed: | Yes |
Identification Number: | 10.3233/blc-220076 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:217531 |