Evidence map›Paper›PMID 42706231›Full record

SynthesisNature communications2026

Multi-population GWAS meta-analysis identifies bladder cancer susceptibility loci and highlights genetic regulation of smoking-related risk.

Ludmila Prokunina-Olsson, Oscar Florez-Vargas, Michael G Levin, Diptavo Dutta, Charles E Breeze, Lauren M Hurwitz, Wusheng Yan, Philippe Lamy, Brenen W Papenberg, Kevin Wang and 48 more

Abstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

58 authors.

Ludmila Prokunina-Olsson *Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA. prokuninal@mail.nih.gov.ORCID http://orcid.org/0000-0002-9622-2091
Oscar Florez-Vargas *Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-4393-2612
Michael G Levin *Department of Medicine, Division of Cardiovascular Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-9937-9932
Diptavo DuttaIntegrative Tumor Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-6634-9040
Charles E BreezeOccupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-5294-915X
Lauren M HurwitzOccupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.ORCID http://orcid.org/0000-0001-8932-5028
Wusheng YanLaboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-4722-1156
Philippe LamyDepartment of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark.
Brenen W PapenbergLaboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.ORCID http://orcid.org/0000-0003-3734-3018
Kevin WangIntegrative Tumor Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
Chia-Han LeeCancer Genomics Research Laboratory, Frederick National Laboratory for Cancer Research, Rockville, MD, USA.
Roger L MilneCancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC, Australia.ORCID http://orcid.org/0000-0001-5764-7268
Jian GuUniversity of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0003-3499-0973
Caroline Y UmPopulation Science, American Cancer Society, Atlanta, GA, USA.ORCID http://orcid.org/0000-0001-5449-6230
Vijai JosephMemorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID http://orcid.org/0000-0002-7933-151X
Helena FurbergMemorial Sloan Kettering Cancer Center, New York, NY, USA.
Florence Le Calvez-KelmGenomic Epidemiology Branch, International Agency for Research on Cancer, Lyon, France.ORCID http://orcid.org/0000-0003-0063-5068
Adriana LoriPopulation Science, American Cancer Society, Atlanta, GA, USA.
Parichoy Pal ChoudhurySurveillance, Prevention, & Health Services Research, American Cancer Society, Atlanta, GA, USA.ORCID http://orcid.org/0000-0002-7072-0535
Nina AfsharCancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC, Australia.ORCID http://orcid.org/0000-0001-5587-9540
Manolis KogevinasISGlobal, Barcelona, Spain.
Kenneth OffitMemorial Sloan Kettering Cancer Center, New York, NY, USA.
Sita H VermeulenScience Department IQ Health & Urology, Radboud University Medical Center, Nijmegen, Netherlands.ORCID http://orcid.org/0000-0003-4913-8601
Evangelina López de MaturanaGenetic and Molecular Epidemiology Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.ORCID http://orcid.org/0000-0001-9425-3911
Demetrius AlbanesMetabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
Mark P PurdueOccupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
Victoria K CortessisDepartment of Population and Public Health Sciences, Epidemiology and Genetics, University of Southern California, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0002-2339-1089
Margaret R KaragasDepartment of Epidemiology, Geisel School of Medicine at Dartmouth, Hanover, NH, USA.ORCID http://orcid.org/0000-0002-6398-7362
Charles KooperbergDivision of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-7986-8560
Marc BjurlinDepartment of Urology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Deborah A TadesseOccupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
Steven C MooreMetabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-8169-1661
Wen-Yi HuangMetabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-4440-3368
Christopher A HaimanCenter for Genetic Epidemiology, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0002-0097-9971
Mariana C SternDepartment of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
A Heather EliassenChanning Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-3961-6609
Lorelei A MucciDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Katja K AbenScience Department IQ Health & Urology, Radboud University Medical Center, Nijmegen, Netherlands.ORCID http://orcid.org/0000-0002-0214-2147
Tessel E GaleslootScience Department IQ Health & Urology, Radboud University Medical Center, Nijmegen, Netherlands.
UROMOL Consortium
Anurag VermaDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-5063-9107
Soichiro YoshinoLaboratory for Statistical and Translational Genetics, Center for Integrative Medical Sciences, RIKEN, Yokohama, Japan.
Keiko HikinoLaboratory for Pharmacogenomics, Center for Integrative Medical Sciences, RIKEN, Yokohama, Japan.ORCID http://orcid.org/0000-0002-4852-2401
Chikashi TeraoLaboratory for Statistical and Translational Genetics, Center for Integrative Medical Sciences, RIKEN, Yokohama, Japan.ORCID http://orcid.org/0000-0002-6452-4095
Thorunn RafnarAmgen deCODE Genetics, Reykjavik, Iceland.
Koichi MatsudaLaboratory of Clinical Genome Sequencing, Graduate school of Frontier Science, University of Tokyo, Tokyo, Japan.ORCID http://orcid.org/0000-0001-7292-2686
Taro ShuinDepartment of Urology, School of Medicine, Kochi University, Nankoku, Japan.
Montserrat Garcia-ClosasCancer Epidemiology and Prevention Research Unit, Institute of Cancer Research, Imperial College London, London, UK.
Francisco X RealEpithelial Carcinogenesis Group, Spanish National Cancer Research Centre (CNIO) and CIBERONC, Madrid, Spain.
Lambertus A KiemeneyScience Department IQ Health & Urology, Radboud University Medical Center, Nijmegen, Netherlands.
Stephen J ChanockOffice of the Director, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
Núria MalatsGenetic and Molecular Epidemiology Group, Spanish National Cancer Research Centre (CNIO) and CIBERONC, Madrid, Spain.
Debra T SilvermanOccupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
Lars DyrskjotDepartment of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark.
Nathaniel RothmanOccupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
Scott M DamrauerDepartment of Surgery, Corporal Michael Crescenz VA Medical Center, Philadelphia, PA, USA.
Stella KoutrosOccupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
Jeffrey S DamrauerLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. jeffrey_damrauer@med.unc.edu.

Funding

Doris Duke Charitable Foundation (DDCF) 2023-0224
6 · The paper itself

Abstract

Bladder cancer is the ninth most common cancer worldwide, caused by genetic and environmental risk factors. Here, we report the findings of a multi-population meta-analysis of genome-wide association studies, including 32,470 individuals with and 1,753,462 without bladder cancer. We identify 70 independent risk loci, of which 43 are novel. Using a 70-marker polygenic risk score (HR = 1.63 per standard deviation), we increase the area under the curve from 0.71 (baseline risk model) to 0.75. Integrative analyses reveal the enrichment of the associated variants within accessible chromatin regions, and of the prioritized genes within pathways for xenobiotic metabolism and smoking behavior. Specifically, we show that the 15q25.1 variant rs71581744-ACCCC/A co-localizes with tissue-specific CHRNA3 expression, modulates mRNA stability, and associates with risk of muscle-invasive bladder cancer among current smokers. Together, these findings substantially expand the known genetic architecture of bladder cancer risk and highlight the germline regulation of smoking behavior as a mechanism driving bladder cancer susceptibility.

Indexed as

Genetic Predisposition to DiseaseSmokingUrinary Bladder NeoplasmsChromosomes, Human, Pair 15Gene Expression Regulation, NeoplasticGenetic LociGenetic Risk ScoreGenome-Wide Association StudyHumansPolymorphism, Single NucleotideReceptors, NicotinicRisk FactorsReceptors, Nicotinic

Identifiers

PMID42706231
PMCPMC13550465

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.