Student and Faculty Publications

Authors

Stella Koutros
Lambertus A Kiemeney
Parichoy Pal Choudhury
Roger L Milne
Evangelina Lopez de Maturana
Yuanqing Ye
Vijai Joseph
Oscar Florez-Vargas
Lars Dyrskjøt
Jonine Figueroa
Diptavo Dutta
Graham G Giles
Michelle A T Hildebrandt
Kenneth Offit
Manolis Kogevinas
Elisabete Weiderpass
Marjorie L McCullough
Neal D Freedman
Demetrius Albanes
Charles Kooperberg
Victoria K Cortessis
Margaret R Karagas
Alison Johnson
Molly R Schwenn
Dalsu Baris
Helena Furberg
Dean F Bajorin
Olivier Cussenot
Geraldine Cancel-Tassin
Simone Benhamou
Peter Kraft
Stefano Porru
Angela Carta
Timothy Bishop
Melissa C Southey
Giuseppe Matullo
Tony Fletcher
Rajiv Kumar
Jack A Taylor
Philippe Lamy
Frederik Prip
Mark Kalisz
Stephanie J Weinstein
Jan G Hengstler
Silvia Selinski
Mark Harland
Mark Teo
Anne E Kiltie
Adonina Tardón
Consol Serra
Alfredo Carrato
Reina García-Closas
Josep Lloreta
Alan Schned
Petra Lenz
Elio Riboli
Paul Brennan
Anne Tjønneland
Thomas Otto
Daniel Ovsiannikov
Frank Volkert
Sita H Vermeulen
Katja K Aben
Tessel E Galesloot
Constance Turman
Immaculata De Vivo
Edward Giovannucci
David J Hunter
Chancellor Hohensee
Rebecca Hunt
Alpa V Patel
Wen-Yi Huang
Gudmar Thorleifsson
Manuela Gago-Dominguez
Pilar Amiano
Klaus Golka
Mariana C Stern
Wusheng Yan
Jia Liu
Shengchao Alfred Li
Shilpa Katta
Amy Hutchinson
Belynda Hicks
William A Wheeler
Mark P Purdue
Katherine A McGlynn
Cari M Kitahara
Christopher A Haiman
Mark H Greene
Thorunn Rafnar
Nilanjan Chatterjee
Stephen J Chanock
Xifeng Wu
Francisco X Real
Debra T Silverman
Montserrat Garcia-Closas
Kari Stefansson
Ludmila Prokunina-Olsson
Núria Malats
Nathaniel Rothman

Publication Date

7-1-2023

Journal

European Urology

Abstract

BACKGROUND: Genomic regions identified by genome-wide association studies (GWAS) for bladder cancer risk provide new insights into etiology.

OBJECTIVE: To identify new susceptibility variants for bladder cancer in a meta-analysis of new and existing genome-wide genotype data.

DESIGN, SETTING, AND PARTICIPANTS: Data from 32 studies that includes 13,790 bladder cancer cases and 343,502 controls of European ancestry were used for meta-analysis.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSES: Log-additive associations of genetic variants were assessed using logistic regression models. A fixed-effects model was used for meta-analysis of the results. Stratified analyses were conducted to evaluate effect modification by sex and smoking status. A polygenic risk score (PRS) was generated on the basis of known and novel susceptibility variants and tested for interaction with smoking.

RESULTS AND LIMITATIONS: Multiple novel bladder cancer susceptibility loci (6p.22.3, 7q36.3, 8q21.13, 9p21.3, 10q22.1, 19q13.33) as well as improved signals in three known regions (4p16.3, 5p15.33, 11p15.5) were identified, bringing the number of independent markers at genome-wide significance (p < 5 × 10

CONCLUSIONS: We report novel loci associated with risk of bladder cancer that provide clues to its biological underpinnings. Using 24 independent markers, we constructed a PRS to stratify lifetime risk. The PRS combined with smoking history, and other established risk factors, has the potential to inform future screening efforts for bladder cancer.

PATIENT SUMMARY: We identified new genetic markers that provide biological insights into the genetic causes of bladder cancer. These genetic risk factors combined with lifestyle risk factors, such as smoking, may inform future preventive and screening strategies for bladder cancer.

Keywords

Male, Humans, Female, Genome-Wide Association Study, Prospective Studies, Risk Factors, Genotype, Urinary Bladder Neoplasms, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Arylamine N-Acetyltransferase, Microtubule-Associated Proteins, Membrane Proteins, Adaptor Proteins, Signal Transducing

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