TGFB1 and TGFBR1 polymorphic variants in relationship to bladder cancer risk and prognosis

Authors

  • Adela Castillejo,

    1. Grupo de Oncología Molecular, Hospital General Universitario de Elche, Elche, Spain
    Search for more papers by this author
  • Nathaniel Rothman,

    1. Department of Health and Human Services, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD
    Search for more papers by this author
  • Cristiane Murta-Nascimento,

    1. Programa de Recerca en Càncer, Institut Municipal d'Investigació Mèdica (IMIM-Hospital del Mar), Barcelona, Spain
    2. Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain
    Search for more papers by this author
  • Núria Malats,

    1. Programa de Recerca en Càncer, Institut Municipal d'Investigació Mèdica (IMIM-Hospital del Mar), Barcelona, Spain
    2. Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain
    3. Programas de Genética del Cáncer Humano y Patología Molecular, Centro Nacional de Investigaciones Oncológicas, Madrid, Spain
    Search for more papers by this author
  • Montserrat García-Closas,

    1. Department of Health and Human Services, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD
    Search for more papers by this author
  • Angeles Gómez-Martínez,

    1. Grupo de Oncología Molecular, Hospital General Universitario de Elche, Elche, Spain
    Search for more papers by this author
  • Josep Lloreta,

    1. Departament de Patologia, Hospital del Mar, Barcelona, Spain
    2. Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain
    Search for more papers by this author
  • Adonina Tardón,

    1. Departamento de Epidemiología y Medicina Preventiva, Universidad de Oviedo, Oviedo, Spain
    2. CIBER en Epidemiología y Salud Pública (CIBERESP), Spain
    Search for more papers by this author
  • Consol Serra,

    1. Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain
    2. Consorci Hospitalari Parc Taulí, Sabadell, Spain
    Search for more papers by this author
  • Reina García-Closas,

    1. Department of Social Medicine, Unidad de Investigación, Hospital Universitario de Canarias, La Laguna, Spain
    Search for more papers by this author
  • Stephen Chanock,

    1. Core Genotype Facility, Advanced Technology Center, National Cancer Institute, Gaithersberg, MD
    Search for more papers by this author
  • Debra T. Silverman,

    1. Department of Health and Human Services, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD
    Search for more papers by this author
  • Mustafa Dosemeci,

    1. Department of Health and Human Services, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD
    Search for more papers by this author
  • Manolis Kogevinas,

    1. Programa de Recerca en Càncer, Institut Municipal d'Investigació Mèdica (IMIM-Hospital del Mar), Barcelona, Spain
    2. Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain
    3. CIBER en Epidemiología y Salud Pública (CIBERESP), Spain
    4. University of Crete, Heraklion, Greece
    Search for more papers by this author
  • Alfredo Carrato,

    1. Grupo de Oncología Molecular, Hospital General Universitario de Elche, Elche, Spain
    Search for more papers by this author
    • Alfredo Carrato, José Luis Soto and Francisco X. Real have contributed equally to this work and share senior authorship.

  • José Luis Soto,

    1. Grupo de Oncología Molecular, Hospital General Universitario de Elche, Elche, Spain
    Search for more papers by this author
    • Alfredo Carrato, José Luis Soto and Francisco X. Real have contributed equally to this work and share senior authorship.

  • Francisco X. Real

    Corresponding author
    1. Programa de Recerca en Càncer, Institut Municipal d'Investigació Mèdica (IMIM-Hospital del Mar), Barcelona, Spain
    2. Programas de Genética del Cáncer Humano y Patología Molecular, Centro Nacional de Investigaciones Oncológicas, Madrid, Spain
    3. Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain
    • Centro Nacional de Investigaciones Oncológicas (CNIO), C/ Melchor Fernández Almagro 3, E-28029 Madrid, Spain
    Search for more papers by this author
    • Alfredo Carrato, José Luis Soto and Francisco X. Real have contributed equally to this work and share senior authorship.


Abstract

The transforming growth factor-beta (TGF-β) signalling pathway plays an important role in tumor development and progression. We aimed at analyzing whether 7 different common variants in genes coding for 2 key members of the TGF-β signalling pathway (TGFB1 and TGFBR1) are associated with bladder cancer risk and prognosis. A total of 1,157 cases with urothelial cell carcinoma of the bladder and 1,157 matched controls where genotyped for 3 single nucleotide polymorphisms (SNPs) in TGFB1 (rs1982073, rs1800472, rs1800471) and an additional 3 SNPs and 1 indel polymorphism in TGFBR1 (rs868, rs928180, rs334358 and rs11466445, respectively). In the case-control study, we estimated odds ratios and 95% confidence intervals for each individual genetic variant using unconditional logistic regression adjusting for age, gender, study area and smoking status. Survival analysis was performed using the Kaplan-Meier method and Cox models. The endpoints of interest were tumor relapse, progression and death from bladder cancer. All the SNPs analyzed showed a similar distribution among cases and controls. The distribution of the TGFBR1*6A allele (rs11466445) was also similar among cases and controls, indicating no association with bladder cancer risk. Similarly, none of the haplotypes was significantly associated with bladder cancer risk. Among patients with muscle-invasive tumors, we found a significant association between TGFBR1-rs868 and disease-specific mortality with an allele dosage effect (p-trend = 0.003). In conclusion, the genetic variants analyzed were not associated with an increased risk of bladder cancer. The association of TGFBR1-rs868 with outcome should be validated in independent patient series. © 2008 Wiley-Liss, Inc.

Ancillary