Abstract B15: Bladder cancer susceptibility polymorphisms and mortality from non-muscle and muscle-invasive bladder cancer
Authors: Leeming Reno C. , Zens Michael S. , Seigne John D. , Christensen Brock C. , Gilbert-Diamond Diane , Karagas Margaret R. , Passarelli Michael N. 
Published: August 2020

Abstract
Introduction: Genome-wide association studies (GWAS) have identified several common germline single-nucleotide polymorphisms (SNPs) associated with increased risk of bladder cancer. Little is known about whether these variants are also associated with overall and bladder cancer-specific mortality. We examined the association between 13 GWAS-identified bladder cancer risk SNPs and overall and bladder cancer-specific survival in 316 bladder cancer cases recruited as part of a population-based case-control study.
Methods: Residents of New Hampshire with primary bladder cancer diagnosed between 2002-2004 were identified from the New Hampshire State Cancer Registry. Medical history and lifestyle factors were collected via in-person interviews at time of enrollment. DNA was isolated from peripheral blood or buccal specimens and genotyping was performed using the Illumina Human610-Quad BeadChip. Date and cause of death were ascertained from the National Death Index with follow-up through December 31, 2013. Non-muscle invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC) were examined separately. We used Cox proportional hazards models to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI) for overall and bladder cancer-specific survival, assuming a log-additive genetic model. HR estimates for MIBC individuals were adjusted for age at diagnosis, sex, smoking status, American Joint Committee on Cancer stage, initial treatment (including extent of resection, cystectomy, and use of chemotherapy or radiation), and three principal components for genetic ancestry. HR estimates for NMIBC were additionally adjusted for 2004 World Health Organization/International Society of Urologic Pathologists classification. An alpha of 0.05 was used to determine statistical significance.
Results: Among 43 participants with MIBC, 30 deaths occurred over a median follow-up of 6.4 years, including 19 from bladder cancer. Among 273 participants with NMIBC, 94 deaths occurred over a median follow-up of 10.3 years, including 23 from bladder cancer. The risk allele [A] of enhancer-associated intergenic SNP rs710521 near TP63 was associated with poorer overall survival after MIBC diagnosis (HR=3.21, 95% CI=1.26-8.16). The risk allele [C] of synonymous SNP rs10936599 of MYNN/TERC was associated with better overall survival after NMIBC diagnosis (HR=0.66, 95% CI=0.46-0.94). No associations with bladder cancer-specific survival were identified.
Conclusions: Common bladder cancer susceptibility variants rs710521 and rs10936599 may be associated with overall survival after diagnosis of MIBC and NMIBC, respectively.
Citation Format: Reno C. Leeming, Michael S. Zens, John D. Seigne, Brock C. Christensen, Diane Gilbert-Diamond, Margaret R. Karagas, Michael N. Passarelli. Bladder cancer susceptibility polymorphisms and mortality from non-muscle and muscle-invasive bladder cancer [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2019 May 18-21; Denver, CO. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(15_Suppl):Abstract nr B15.