title: The 19q12 bladder cancer GWAS signal: association with cyclin E function and aggressive disease.
abstract: A genome-wide association study (GWAS) of bladder cancer identified a genetic marker rs8102137 within the 19q12 region as a novel susceptibility variant. This marker is located upstream of the CCNE1 gene, which encodes cyclin E, a cell-cycle protein. We performed genetic fine-mapping analysis of the CCNE1 region using data from two bladder cancer GWAS (5,942 cases and 10,857 controls). We found that the original GWAS marker rs8102137 represents a group of 47 linked SNPs (with r(2) ≥ 0.7) associated with increased bladder cancer risk. From this group, we selected a functional promoter variant rs7257330, which showed strong allele-specific binding of nuclear proteins in several cell lines. In both GWASs, rs7257330 was associated only with aggressive bladder cancer, with a combined per-allele OR = 1.18 [95% confidence interval (CI), 1.09-1.27, P = 4.67 × 10(-5)] versus OR = 1.01 (95% CI, 0.93-1.10, P = 0.79) for nonaggressive disease, with P = 0.0015 for case-only analysis. Cyclin E protein expression analyzed in 265 bladder tumors was increased in aggressive tumors (P = 0.013) and, independently, with each rs7257330-A risk allele (P(trend) = 0.024). Overexpression of recombinant cyclin E in cell lines caused significant acceleration of cell cycle. In conclusion, we defined the 19q12 signal as the first GWAS signal specific for aggressive bladder cancer. Molecular mechanisms of this genetic association may be related to cyclin E overexpression and alteration of cell cycle in carriers of CCNE1 risk variants. In combination with established bladder cancer risk factors and other somatic and germline genetic markers, the CCNE1 variants could be useful for inclusion into bladder cancer risk prediction models.
authors.affiliation: Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Yi-Ping
authors.initials: YP
authors.lastname: Fu
authors.affiliation: Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Indu
authors.initials: I
authors.lastname: Kohaar
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Lee E
authors.initials: LE
authors.lastname: Moore
authors.affiliation: Clinical Research Directorate/Clinical Monitoring Research Program, SAIC-Frederick, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland.
authors.forename: Petra
authors.initials: P
authors.lastname: Lenz
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Jonine D
authors.initials: JD
authors.lastname: Figueroa
authors.affiliation: Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Wei
authors.initials: W
authors.lastname: Tang
authors.affiliation: Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Patricia
authors.initials: P
authors.lastname: Porter-Gill
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Nilanjan
authors.initials: N
authors.lastname: Chatterjee
authors.affiliation: Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Scott-Johnson
authors.affiliation: Division of Genetics and Epidemiology, Institute of Cancer Research, London, United Kingdom.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Garcia-Closas
authors.affiliation: Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Brian
authors.initials: B
authors.lastname: Muchmore
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Dalsu
authors.initials: D
authors.lastname: Baris
authors.affiliation: Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Ashley
authors.initials: A
authors.lastname: Paquin
authors.affiliation: Laboratory of Pathology, Center of Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Kris
authors.initials: K
authors.lastname: Ylaya
authors.affiliation: Maine Cancer Registry, Augusta, Maine.
authors.forename: Molly
authors.initials: M
authors.lastname: Schwenn
authors.affiliation: Genitourinary Malignancy Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland.
authors.forename: Andrea B
authors.initials: AB
authors.lastname: Apolo
authors.affiliation: Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire.
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Karagas
authors.affiliation: Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: McAnthony
authors.initials: M
authors.lastname: Tarway
authors.affiliation: Vermont Cancer Registry, Burlington, Vermont.
authors.forename: Alison
authors.initials: A
authors.lastname: Johnson
authors.affiliation: Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Adam
authors.initials: A
authors.lastname: Mumy
authors.affiliation: Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire.
authors.forename: Alan
authors.initials: A
authors.lastname: Schned
authors.affiliation: Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Liliana
authors.initials: L
authors.lastname: Guedez
authors.affiliation: Department of Pathology and Laboratory Medicine, Maine Medical Center, Portland, Maine.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Jones
authors.affiliation: Department of Pathology, University of Vermont College of Medicine, Burlington, Vermont.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Kida
authors.affiliation: New Hampshire State Cancer Registry, Concord, New Hampshire.
authors.forename: G M Monawar
authors.initials: GM
authors.lastname: Hosain
authors.affiliation: Spanish National Cancer Research Centre, Madrid, Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: Malats
authors.affiliation: Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain. Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain. National School of Public Health, Athens, Greece. CIBER Epidemiologia y Salud Pública (CIBERESP), Barcelona, Spain.
authors.forename: Manolis
authors.initials: M
authors.lastname: Kogevinas
authors.affiliation: CIBER Epidemiologia y Salud Pública (CIBERESP), Barcelona, Spain. Instituto Universitario de Oncología, Universidad de Oviedo, Oviedo, Spain.
authors.forename: Adonina
authors.initials: A
authors.lastname: Tardon
authors.affiliation: CIBER Epidemiologia y Salud Pública (CIBERESP), Barcelona, Spain. Universitat Pompeu Fabra, Barcelona, Spain.
authors.forename: Consol
authors.initials: C
authors.lastname: Serra
authors.affiliation: Ramón y Cajal Hospital, Madrid, Spain.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Carrato
authors.affiliation: Unidad de Investigación, Hospital Universitario de Canarias, La Laguna, Spain.
authors.forename: Reina
authors.initials: R
authors.lastname: Garcia-Closas
authors.affiliation: Hospital del Mar-IMIM, Univesitat Pompeu Fabra, Barcelona, Spain.
authors.forename: Josep
authors.initials: J
authors.lastname: Lloreta
authors.affiliation: Department of Epidemiology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas.
authors.forename: Xifeng
authors.initials: X
authors.lastname: Wu
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Mark
authors.initials: M
authors.lastname: Purdue
authors.affiliation: Division of Urologic Surgery, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Gerald L
authors.initials: GL
authors.lastname: Andriole
authors.affiliation: Division of Urologic Surgery, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Grubb
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Amanda
authors.initials: A
authors.lastname: Black
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Maria T
authors.initials: MT
authors.lastname: Landi
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Neil E
authors.initials: NE
authors.lastname: Caporaso
authors.affiliation: School of Public Health, Imperial College London, London, United Kingdom. Human Genetics Foundation (HuGeF), Torino, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Vineis
authors.affiliation: School of Public Health, Imperial College London, London, United Kingdom.
authors.forename: Afshan
authors.initials: A
authors.lastname: Siddiq
authors.affiliation: National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands. Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, the Netherlands. Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, London, United Kingdom. Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: H Bas
authors.initials: HB
authors.lastname: Bueno-de-Mesquita
authors.affiliation: Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts. Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece. Hellenic Health Foundation, Athens, Greece.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Trichopoulos
authors.affiliation: Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, Umeå, Sweden.
authors.forename: Börje
authors.initials: B
authors.lastname: Ljungberg
authors.affiliation: Human Genetics Foundation (HuGeF), Torino, Italy. Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia. Centre for Epidemiology and Biostatistics, University of Melbourne, Australia.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Severi
authors.affiliation: Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway. Department of Research, Cancer Registry of Norway, Oslo, Norway. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. Samfundet Folkhälsan, Helsinki, Finland.
authors.forename: Elisabete
authors.initials: E
authors.lastname: Weiderpass
authors.affiliation: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Krogh
authors.affiliation: Public Health Division of Gipuzkoa, Basque Regional Health Department and Ciberesp-Biodonostia, San Sebastian, Spain.
authors.forename: Miren
authors.initials: M
authors.lastname: Dorronsoro
authors.affiliation: Cancer Epidemiology Unit, University of Oxford, Oxford, United Kingdom.
authors.forename: Ruth C
authors.initials: RC
authors.lastname: Travis
authors.affiliation: Danish Cancer Society Research Center, Copenhagen, Denmark.
authors.forename: Anne
authors.initials: A
authors.lastname: Tjønneland
authors.affiliation: International Agency for Research on Cancer, Lyon, France.
authors.forename: Paul
authors.initials: P
authors.lastname: Brennan
authors.affiliation: Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Jenny
authors.initials: J
authors.lastname: Chang-Claude
authors.affiliation: School of Public Health, Imperial College London, London, United Kingdom.
authors.forename: Elio
authors.initials: E
authors.lastname: Riboli
authors.affiliation: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. Program in Genetic Epidemiology and Statistical Genetics, Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Prescott
authors.affiliation: Program in Genetic Epidemiology and Statistical Genetics, Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts.
authors.forename: Constance
authors.initials: C
authors.lastname: Chen
authors.affiliation: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. Program in Genetic Epidemiology and Statistical Genetics, Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts.
authors.forename: Immaculata
authors.initials: I
authors.lastname: De Vivo
authors.affiliation: Department of Nutrition and Epidemiology, Harvard School of Public Health, Boston, Massachusetts.
authors.forename: Edward
authors.initials: E
authors.lastname: Govannucci
authors.affiliation: Program in Genetic Epidemiology and Statistical Genetics, Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts.
authors.forename: David
authors.initials: D
authors.lastname: Hunter
authors.affiliation: Program in Genetic Epidemiology and Statistical Genetics, Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts.
authors.forename: Peter
authors.initials: P
authors.lastname: Kraft
authors.affiliation: Program in Genetic Epidemiology and Statistical Genetics, Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts.
authors.forename: Sara
authors.initials: S
authors.lastname: Lindstrom
authors.affiliation: Epidemiology Research Program, American Cancer Society, Atlanta, Georgia.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Gapstur
authors.affiliation: Epidemiology Research Program, American Cancer Society, Atlanta, Georgia.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Jacobs
authors.affiliation: Epidemiology Research Program, American Cancer Society, Atlanta, Georgia.
authors.forename: W Ryan
authors.initials: WR
authors.lastname: Diver
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Demetrius
authors.initials: D
authors.lastname: Albanes
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Weinstein
authors.affiliation: National Institute for Health and Welfare, Helsinki, Finland.
authors.forename: Jarmo
authors.initials: J
authors.lastname: Virtamo
authors.affiliation: Fred Hutchinson Cancer Research Center, Division of Public Health Sciences, Seattle, Washington.
authors.forename: Charles
authors.initials: C
authors.lastname: Kooperberg
authors.affiliation: Fred Hutchinson Cancer Research Center, Division of Public Health Sciences, Seattle, Washington.
authors.forename: Chancellor
authors.initials: C
authors.lastname: Hohensee
authors.affiliation: Fred Hutchinson Cancer Research Center, Division of Public Health Sciences, Seattle, Washington.
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Rodabough
authors.affiliation: Department of Obstetrics and Gynecology, Keck School of Medicine of USC, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California. Department of Preventive Medicine, Keck School of Medicine of USC, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California.
authors.forename: Victoria K
authors.initials: VK
authors.lastname: Cortessis
authors.affiliation: Department of Preventive Medicine, Keck School of Medicine of USC, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California.
authors.forename: David V
authors.initials: DV
authors.lastname: Conti
authors.affiliation: Genomic Medicine Group, Galician Foundation of Genomic Medicine, Complejo Hospitalario Universitario de Santiago, Servicio Galego de Saude (SERGAS), Instituto de Investigación Sanitaria de Santiago (IDIS), Santiago de Compostela, Spain.
authors.forename: Manuela
authors.initials: M
authors.lastname: Gago-Dominguez
authors.affiliation: Department of Preventive Medicine, Keck School of Medicine of USC, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California.
authors.forename: Mariana C
authors.initials: MC
authors.lastname: Stern
authors.affiliation: Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York.
authors.forename: Malcolm C
authors.initials: MC
authors.lastname: Pike
authors.affiliation: Department of Preventive Medicine, Keck School of Medicine of USC, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California.
authors.forename: David
authors.initials: D
authors.lastname: Van Den Berg
authors.affiliation: University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania.
authors.forename: Jian-Min
authors.initials: JM
authors.lastname: Yuan
authors.affiliation: Department of Preventive Medicine, Keck School of Medicine of USC, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Haiman
authors.affiliation: AP-HP, Hopital Tenon, GHU-Est, Department of Urology, Paris, France. Centre de Recherche sur les Pathologies Prostatiques, Paris, France. UPMC Univ Paris 06, ONCOTYPE-URO, Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Cussenot
authors.affiliation: Centre de Recherche sur les Pathologies Prostatiques, Paris, France. UPMC Univ Paris 06, ONCOTYPE-URO, Paris, France.
authors.forename: Geraldine
authors.initials: G
authors.lastname: Cancel-Tassin
authors.affiliation: Centre de Recherche sur les Pathologies Prostatiques, Paris, France. UPMC Univ Paris 06, ONCOTYPE-URO, Paris, France. AP-HP, Hopital Pitie-Salpetriere, GHU-Est, Departments of Urology and Pathology, Paris, France.
authors.forename: Morgan
authors.initials: M
authors.lastname: Roupret
authors.affiliation: Centre de Recherche sur les Pathologies Prostatiques, Paris, France. UPMC Univ Paris 06, ONCOTYPE-URO, Paris, France. AP-HP, Hopital Pitie-Salpetriere, GHU-Est, Departments of Urology and Pathology, Paris, France.
authors.forename: Eva
authors.initials: E
authors.lastname: Comperat
authors.affiliation: Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Porru
authors.affiliation: Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Carta
authors.affiliation: Department of Cardiac, Thoracic and Vascular Sciences, University of Padova, Padua, Italy.
authors.forename: Sofia
authors.initials: S
authors.lastname: Pavanello
authors.affiliation: Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Arici
authors.affiliation: Department of Cardiac, Thoracic and Vascular Sciences, University of Padova, Padua, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Mastrangelo
authors.affiliation: Department of Urology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas.
authors.forename: H Barton
authors.initials: HB
authors.lastname: Grossman
authors.affiliation: Cancer Genomics Research Laboratory, SAIC-Frederick, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland.
authors.forename: Zhaoming
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Cancer Genomics Research Laboratory, SAIC-Frederick, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland.
authors.forename: Xiang
authors.initials: X
authors.lastname: Deng
authors.affiliation: Cancer Genomics Research Laboratory, SAIC-Frederick, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland.
authors.forename: Charles C
authors.initials: CC
authors.lastname: Chung
authors.affiliation: Cancer Genomics Research Laboratory, SAIC-Frederick, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland.
authors.forename: Amy
authors.initials: A
authors.lastname: Hutchinson
authors.affiliation: Cancer Genomics Research Laboratory, SAIC-Frederick, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland.
authors.forename: Laurie
authors.initials: L
authors.lastname: Burdette
authors.affiliation: Information Management Services, Rockville, Maryland.
authors.forename: William
authors.initials: W
authors.lastname: Wheeler
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Joseph
authors.initials: J
authors.lastname: Fraumeni
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Chanock
authors.affiliation: Laboratory of Pathology, Center of Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Hewitt
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Debra T
authors.initials: DT
authors.lastname: Silverman
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Rothman
authors.affiliation: Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland. prokuninal@mail.nih.gov.
authors.forename: Ludmila
authors.initials: L
authors.lastname: Prokunina-Olsson
mesh_terms: D016022:Case-Control Studies; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics*; D019927:Cyclin E / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D005787:Gene Frequency; D055106:Genome-Wide Association Study; D006239:Haplotypes; D006367:HeLa Cells; D006801:Humans; D015513:Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D001743:Urinary Bladder / Q000378:metabolism / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: C475820:CCNE1 protein, human; D019927:Cyclin E; D015513:Oncogene Proteins