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

Adela Castillejo, Nathaniel Rothman, Cristiane Murta-Nascimento, Núria Malats, Montserrat García-Closas, Angeles Gómez-Martínez, Josep Lloreta, Adonina Tardón, Consol Serra, Reina García-Closas, Stephen Chanock, Debra T. Silverman, Mustafa Dosemeci, Manolis Kogevinas, Alfredo Carrato, José Luis Soto, Francisco X. Real

Research output: Contribution to journalArticle

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 al- lele (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.

Original languageEnglish (US)
Pages (from-to)608-613
Number of pages6
JournalInternational Journal of Cancer
Volume124
Issue number3
DOIs
StatePublished - Feb 1 2009
Externally publishedYes

Fingerprint

Urinary Bladder Neoplasms
Single Nucleotide Polymorphism
Transforming Growth Factor beta
Alleles
Neoplasms
Survival Analysis
Proportional Hazards Models
Haplotypes
Case-Control Studies
Urinary Bladder
Logistic Models
Smoking
Odds Ratio
Confidence Intervals
Carcinoma
Recurrence
Muscles
Mortality
Genes

Keywords

  • Genetic susceptibility
  • Prognosis
  • Progression
  • Recurrence
  • Survival
  • Transforming growth factor β
  • Transforming growth factor-β receptor
  • Urinary bladder cancer

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

Castillejo, A., Rothman, N., Murta-Nascimento, C., Malats, N., García-Closas, M., Gómez-Martínez, A., ... Real, F. X. (2009). TGFB1 and TGFBR1 polymorphic variants in relationship to bladder cancer risk and prognosis. International Journal of Cancer, 124(3), 608-613. https://doi.org/10.1002/ijc.24013

TGFB1 and TGFBR1 polymorphic variants in relationship to bladder cancer risk and prognosis. / Castillejo, Adela; Rothman, Nathaniel; Murta-Nascimento, Cristiane; Malats, Núria; García-Closas, Montserrat; Gómez-Martínez, Angeles; Lloreta, Josep; Tardón, Adonina; Serra, Consol; García-Closas, Reina; Chanock, Stephen; Silverman, Debra T.; Dosemeci, Mustafa; Kogevinas, Manolis; Carrato, Alfredo; Soto, José Luis; Real, Francisco X.

In: International Journal of Cancer, Vol. 124, No. 3, 01.02.2009, p. 608-613.

Research output: Contribution to journalArticle

Castillejo, A, Rothman, N, Murta-Nascimento, C, Malats, N, García-Closas, M, Gómez-Martínez, A, Lloreta, J, Tardón, A, Serra, C, García-Closas, R, Chanock, S, Silverman, DT, Dosemeci, M, Kogevinas, M, Carrato, A, Soto, JL & Real, FX 2009, 'TGFB1 and TGFBR1 polymorphic variants in relationship to bladder cancer risk and prognosis', International Journal of Cancer, vol. 124, no. 3, pp. 608-613. https://doi.org/10.1002/ijc.24013
Castillejo A, Rothman N, Murta-Nascimento C, Malats N, García-Closas M, Gómez-Martínez A et al. TGFB1 and TGFBR1 polymorphic variants in relationship to bladder cancer risk and prognosis. International Journal of Cancer. 2009 Feb 1;124(3):608-613. https://doi.org/10.1002/ijc.24013
Castillejo, Adela ; Rothman, Nathaniel ; Murta-Nascimento, Cristiane ; Malats, Núria ; García-Closas, Montserrat ; Gómez-Martínez, Angeles ; Lloreta, Josep ; Tardón, Adonina ; Serra, Consol ; García-Closas, Reina ; Chanock, Stephen ; Silverman, Debra T. ; Dosemeci, Mustafa ; Kogevinas, Manolis ; Carrato, Alfredo ; Soto, José Luis ; Real, Francisco X. / TGFB1 and TGFBR1 polymorphic variants in relationship to bladder cancer risk and prognosis. In: International Journal of Cancer. 2009 ; Vol. 124, No. 3. pp. 608-613.
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AU - García-Closas, Montserrat

AU - Gómez-Martínez, Angeles

AU - Lloreta, Josep

AU - Tardón, Adonina

AU - Serra, Consol

AU - García-Closas, Reina

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AU - Dosemeci, Mustafa

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