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Genome-wide Association Study of Bladder Cancer Reveals New Biological and Translational Insights.
Koutros, Stella; Kiemeney, Lambertus A; Pal Choudhury, Parichoy; Milne, Roger L; Lopez de Maturana, Evangelina; Ye, Yuanqing; Joseph, Vijai; Florez-Vargas, Oscar; Dyrskjøt, Lars; Figueroa, Jonine; Dutta, Diptavo; Giles, Graham G; Hildebrandt, Michelle A T; Offit, Kenneth; Kogevinas, Manolis; Weiderpass, Elisabete; McCullough, Marjorie L; Freedman, Neal D; Albanes, Demetrius; Kooperberg, Charles; Cortessis, Victoria K; Karagas, Margaret R; Johnson, Alison; Schwenn, Molly R; Baris, Dalsu; Furberg, Helena; Bajorin, Dean F; Cussenot, Olivier; Cancel-Tassin, Geraldine; Benhamou, Simone; Kraft, Peter; Porru, Stefano; Carta, Angela; Bishop, Timothy; Southey, Melissa C; Matullo, Giuseppe; Fletcher, Tony; Kumar, Rajiv; Taylor, Jack A; Lamy, Philippe; Prip, Frederik; Kalisz, Mark; Weinstein, Stephanie J; Hengstler, Jan G; Selinski, Silvia; Harland, Mark; Teo, Mark; Kiltie, Anne E; Tardón, Adonina; Serra, Consol.
Affiliation
  • Koutros S; Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA. Electronic address: koutross@mail.nih.gov.
  • Kiemeney LA; Department for Health Evidence, Radboud University Medical Center, Nijmegen, The Netherlands.
  • Pal Choudhury P; Trans-Divisional Research Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA; American Cancer Society, Atlanta, GA, USA.
  • Milne RL; Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Australia; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Australia; Precision Medicine, School of Clinical Sciences at Monash Health, Monash Univer
  • Lopez de Maturana E; Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Centre (CNIO) and CIBERONC, Madrid, Spain.
  • Ye Y; Zhejiang University, Hangzhou, China.
  • Joseph V; Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Florez-Vargas O; Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
  • Dyrskjøt L; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
  • Figueroa J; Usher Institute, University of Edinburgh, Edinburgh, UK; Integrative Tumor Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
  • Dutta D; Integrative Tumor Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
  • Giles GG; Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Australia; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Australia; Precision Medicine, School of Clinical Sciences at Monash Health, Monash Univer
  • Hildebrandt MAT; University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Offit K; Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Kogevinas M; Instituto de Salud Global, Barcelona, Spain.
  • Weiderpass E; International Agency for Research on Cancer, Lyon, France.
  • McCullough ML; Population Science, American Cancer Society, Atlanta, GA, USA.
  • Freedman ND; Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
  • Albanes D; Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
  • Kooperberg C; Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, WA, USA.
  • Cortessis VK; Department of Population and Public Health Sciences, Epidemiology and Genetics, University of Southern California, Los Angeles, CA, USA.
  • Karagas MR; Department of Epidemiology, Geisel School of Medicine at Dartmouth, Hanover, NH, USA.
  • Johnson A; Vermont Department of Health, Burlington, VT, USA.
  • Schwenn MR; Retired, Maine Cancer Registry, Augusta, ME, USA.
  • Baris D; Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
  • Furberg H; Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Bajorin DF; Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Cussenot O; Centre de Recherche sur les Pathologies Prostatiques et Urologiques, Paris, France.
  • Cancel-Tassin G; Centre de Recherche sur les Pathologies Prostatiques et Urologiques, Paris, France; GRC 5 Predictive Onco-Urology, Sorbonne University, Paris, France.
  • Benhamou S; INSERM U1018, Research Centre on Epidemiology and Population Health, Villejuif, France.
  • Kraft P; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
  • Porru S; Department of Diagnostics and Public Health, Section of Occupational Medicine, University of Verona, Verona, Italy.
  • Carta A; Department of Diagnostics and Public Health, Section of Occupational Medicine, University of Verona, Verona, Italy.
  • Bishop T; Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK.
  • Southey MC; Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Australia; Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Australia; Department of Clinical Pathology, The University of Melbourne, Parkville, Australia.
  • Matullo G; Department of Medical Sciences, University of Turin, Turin, Italy.
  • Fletcher T; London School of Hygiene and Tropical Medicine, London, UK.
  • Kumar R; Division of Functional Genome Analysis, German Cancer Research Center, Heidelberg, Germany.
  • Taylor JA; Epidemiology Branch and Epigenetic and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA.
  • Lamy P; Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark.
  • Prip F; Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark.
  • Kalisz M; Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre (CNIO) and CIBERONC, Madrid, Spain.
  • Weinstein SJ; Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
  • Hengstler JG; Leibniz Research Centre for Working Environment and Human Factors at TU Dortmund (IfADo), Dortmund, Germany.
  • Selinski S; Leibniz Research Centre for Working Environment and Human Factors at TU Dortmund (IfADo), Dortmund, Germany.
  • Harland M; Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK.
  • Teo M; Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK.
  • Kiltie AE; Rowett Institute, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, UK.
  • Tardón A; Department of Preventive Medicine, Universidad de Oviedo, ISPA and CIBERESP, Spain.
  • Serra C; Center for Research in Occupational Health, Universitat Pompeu Fabra, Hospital del Mar Medical Research Institut, CIBERESP, Barcelona, Spain.
Eur Urol ; 84(1): 127-137, 2023 07.
Article in En | MEDLINE | ID: mdl-37210288
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 × 10-8) to 24. The 4p16.3 (FGFR3/TACC3) locus was associated with a stronger risk for women than for men (p-interaction = 0.002). Bladder cancer risk was increased by interactions between smoking status and genetic variants at 8p22 (NAT2; multiplicative p value for interaction [pM-I] = 0.004), 8q21.13 (PAG1; pM-I = 0.01), and 9p21.3 (LOC107987026/MTAP/CDKN2A; pM-I = 0.02). The PRS based on the 24 independent GWAS markers (odds ratio per standard deviation increase 1.49, 95% confidence interval 1.44-1.53), which also showed comparable results in two prospective cohorts (UK Biobank, PLCO trial), revealed an approximately fourfold difference in the lifetime risk of bladder cancer according to the PRS (e.g., 1st vs 10th decile) for both smokers and nonsmokers.

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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Arylamine N-Acetyltransferase / Urinary Bladder Neoplasms Type of study: Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Limits: Female / Humans / Male Language: En Journal: Eur Urol Year: 2023 Document type: Article
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Arylamine N-Acetyltransferase / Urinary Bladder Neoplasms Type of study: Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Limits: Female / Humans / Male Language: En Journal: Eur Urol Year: 2023 Document type: Article