Nadezda Lipunova1, Anke Wesselius2, Kar K Cheng3, Frederik-Jan van Schooten4, Richard T Bryan5, Jean-Baptiste Cazier6, Tessel E Galesloot7, Lambertus A L M Kiemeney7, Maurice P Zeegers8. 1. Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK; Department of Complex Genetics, Maastricht University, The Netherlands; Centre for Computational Biology, University of Birmingham, UK. Electronic address: nxl689@student.bham.ac.uk. 2. Department of Complex Genetics, Maastricht University, The Netherlands. 3. Institute for Applied Health Research, University of Birmingham, UK. 4. Department of Pharmacology and Toxicology, Maastricht University, The Netherlands. 5. Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK. 6. Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK; Centre for Computational Biology, University of Birmingham, UK. 7. Radboud University Medical Center, Radboud Institute for Health Sciences, The Netherlands. 8. Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK; Department of Complex Genetics, Maastricht University, The Netherlands.
Abstract
BACKGROUND: Non-muscle-invasive bladder cancer (NMIBC) causes a considerable health burden due to the high recurrence and progression rates. Past studies have identified multiple candidate loci associated with NMIBC prognosis, albeit lacking validation. Moreover, scarce reports exist on genetic susceptibility to independent prognostic predictors of NMIBC, such as stage or grade. OBJECTIVE: To investigate genetic associations with NMIBC tumour and patient characteristics at the time of diagnosis. DESIGN, SETTING, AND PARTICIPANTS: A sample of 653 NMIBC cases comes from the Bladder Cancer Prognosis Programme. Replication of the significant findings was conducted in the Nijmegen Bladder Cancer Study cohort (N=1470). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: A genome-wide association study (GWAS) was carried out for outcomes of tumour size (as a continuous variable in centimetres), stage (Tis and T1 vs Ta), grade (G3 vs G2 and G1), and age (as continuous [years] and dichotomous [70.2 yr as a cut-off] variables). RESULTS AND LIMITATIONS: Significant (p<5E-08) associations (N=61) with tumour size, stage, grade, and age were identified in the GWAS discovery stage. None of the variants were independently significantly associated in the replication cohort. A meta-analysis of both cohorts suggests that rs180940944 (13q13.3 locus, NBEA) was associated with tumour size as a continuous variable (ß=0.9cm, p=2.92E-09). However, other single nucleotide polymorphisms in this region did not show evidence of association in the meta-analysis. CONCLUSIONS: Our study suggests that rs180940944 (NBEA) is associated with an increased NMIBC tumour size at the time of diagnosis. Given study limitations, further replication is essential to validate the finding. PATIENT SUMMARY: The current study reports on a genome-wide association study on non-muscle-invasive bladder cancer tumour and patient characteristics. We suggest that NBEA gene might be associated with increased tumour size at the time of diagnosis. The result must be replicated to establish validity.
BACKGROUND:Non-muscle-invasive bladder cancer (NMIBC) causes a considerable health burden due to the high recurrence and progression rates. Past studies have identified multiple candidate loci associated with NMIBC prognosis, albeit lacking validation. Moreover, scarce reports exist on genetic susceptibility to independent prognostic predictors of NMIBC, such as stage or grade. OBJECTIVE: To investigate genetic associations with NMIBC tumour and patient characteristics at the time of diagnosis. DESIGN, SETTING, AND PARTICIPANTS: A sample of 653 NMIBC cases comes from the Bladder Cancer Prognosis Programme. Replication of the significant findings was conducted in the Nijmegen Bladder Cancer Study cohort (N=1470). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: A genome-wide association study (GWAS) was carried out for outcomes of tumour size (as a continuous variable in centimetres), stage (Tis and T1 vs Ta), grade (G3 vs G2 and G1), and age (as continuous [years] and dichotomous [70.2 yr as a cut-off] variables). RESULTS AND LIMITATIONS: Significant (p<5E-08) associations (N=61) with tumour size, stage, grade, and age were identified in the GWAS discovery stage. None of the variants were independently significantly associated in the replication cohort. A meta-analysis of both cohorts suggests that rs180940944 (13q13.3 locus, NBEA) was associated with tumour size as a continuous variable (ß=0.9cm, p=2.92E-09). However, other single nucleotide polymorphisms in this region did not show evidence of association in the meta-analysis. CONCLUSIONS: Our study suggests that rs180940944 (NBEA) is associated with an increased NMIBC tumour size at the time of diagnosis. Given study limitations, further replication is essential to validate the finding. PATIENT SUMMARY: The current study reports on a genome-wide association study on non-muscle-invasive bladder cancertumour and patient characteristics. We suggest that NBEA gene might be associated with increased tumour size at the time of diagnosis. The result must be replicated to establish validity.
Authors: Nadezda Lipunova; Anke Wesselius; Kar K Cheng; Frederik-Jan van Schooten; Richard T Bryan; Jean-Baptiste Cazier; Maurice P Zeegers Journal: Transl Androl Urol Date: 2020-06
Authors: Nadezda Lipunova; Anke Wesselius; Kar K Cheng; Frederik J van Schooten; Jean-Baptiste Cazier; Richard T Bryan; Maurice P Zeegers Journal: Front Oncol Date: 2019-10-18 Impact factor: 6.244