IBCN 2023: Meta-Analysis of GWAS Data from Diverse Populations for Bladder Cancer (mapBC) Collaboration: Initial Findings

(UroToday.com) To date, the largest genome-wide association study (GWAS) of bladder cancer susceptibility (Koutros, Eur Urol, 2023, NCI-meta) involved a meta-analysis of 13,790 individuals with bladder cancer and reported 24 genome-wide significant (p<5x10-8) loci. While this was a sizable increase over the prior studies, estimates of heritability suggest more loci are yet to be identified.

Using a fixed effects inverse variance weight meta-analysis to combine summary statistics from participating cohorts, case-control studies, and case-series (NCI-meta) and large population biobanks (Million Veterans Program [MVP], UKB, FinnGen), the authors performed a GWAS comprised of 30,136 individuals with and 1,576,084 individuals without bladder cancer.

By doubling the number of individuals with bladder cancer from the previous GWAS, we identified a total of 50 genome-wide significant loci. We replicated all previous risk loci and identified 26 novel loci. Of note, a variant tagging the pathogenic deletion in CHEK2 1100delC (T367Mfs*15) achieved genome-wide significance. Smaller studies had previously implicated CHEK2 in familial bladder cancer, however, this is the first large-scale population-based study to validate this finding in GWAS.

In summary, this study, which is the largest bladder cancer GWAS to date, represents an advancement in the understanding of germline genetic susceptibility for bladder cancer. Analyses are underway to explore possible biological effects of novel GWAS loci. Future efforts will also aim to increase the proportion of individuals of non-European ancestries, that are underrepresented in current efforts.

Presented by: Jeffrey S. Damrauer, Department of Medicine, Division of Oncology, University of North Carolina, Chapel Hill, NC.

Written by: Stephen B. Williams, MD, MBA, MS @SWilliams_MD on Twitter during the International Bladder Cancer Network (IBCN) Annual Meeting, September 29-30, 2023, Montreal, Canada