Inflammatory-related genetic variants in non-muscle-invasive bladder cancer prognosis: A multimarker bayesian assessment

Alexandra Masson-Lecomte, Evangelina López De Maturana, Michael E. Goddard, Antoni Picornell, Marta Rava, Anna González-Neira, Mirari Márquez, Alfredo Carrato, Adonina Tardon, Josep Lloreta, Montserrat Garcia-Closas, Debra Silverman, Nathaniel Rothman, Manolis Kogevinas, Yves Allory, Stephen J. Chanock, Francisco X. Real, Núria Malats, M. Kogevinas, N. MalatsF. X. Real, M. Sala, G. Castano, M. Tora, D. Puente, C. Villanueva, C. Murta-Nascimento, J. Fortuny, E. Lopez, S. Hernandez, R. Jaramillo, G. Vellalta, L. Palencia, F. Fermandez, A. Amoros, A. Alfaro, G. Carretero, J. Lloreta, S. Serrano, L. Ferrer, A. Gelabert, J. Carles, O. Bielsa, K. Villadiego, L. Cecchini, J. M. Saladie, L. Ibarz, M. Cespedes, C. Serra, D. García, J. Pujadas, R. Hernando, A. Cabezuelo, C. Abad, A. Prera, J. Prat, M. Domenech, J. Badal, J. Malet, R. García-Closas, J. Rodríguez De Vera, A. I. Martín, J. Tano, F. Caceres, A. Carrato, F. García-Lopez, M. Ull, A. Teruel, E. Andrada, A. Bustos, A. Castillejo, J. L. Soto, A. Tardon, J. L. Guate, J. M. Lanzas, J. Velasco, J. M. Fernandez, J. J. Rodríguez, A. Herrero, R. Abascal, C. Manzano, T. Miralles, M. Rivas, M. Arguelles, M. Díaz, J. Sanchez, O. Gonzalez, A. Mateos, V. Frade, P. Muntanola, C. Pravia, A. M. Huescar, F. Huergo, J. Mosquera

Research output: Contribution to journalArticle

Abstract

Background: Increasing evidence points to the role of tumor immunologic environment on urothelial bladder cancer prognosis. This effect might be partly dependent on the host genetic context. We evaluated the association of SNPs in inflammationrelated genes with non-muscle-invasive bladder cancer (NMIBC) risk-of-recurrence and risk-of-progression. Methods: We considered 822 NMIBC included in the SBC/ EPICURO Study followed-up >10 years. We selected 1,679 SNPs belonging to 251 inflammatory genes. The association of SNPs with risk-of-recurrence and risk-of-progression was assessed using Cox regression single-marker (SMM) and multimarker methods (MMM) Bayes A and Bayesian LASSO. Discriminative abilities of the models were calculated using the c index and validated with bootstrap cross-validation procedures. Results: While no SNP was found to be associated with risk-ofrecurrence using SMM, three SNPs in TNIP1, CD5, and JAK3 showed very strong association with posterior probabilities >90% using MMM. Regarding risk-of-progression, one SNP in CD3G was significantly associated using SMM (HR, 2.69; P = 1.55 × 10-5) and two SNPs in MASP1 and AIRE, showed a posterior probability ≥80% with MMM. Validated discriminative abilities of the models without and with the SNPs were 58.4% versus 60.5% and 72.1% versus 72.8% for risk-of-recurrence and risk-of-progression, respectively. Conclusions: Using innovative analytic approaches, we demonstrated that SNPs in inflammatory-related genes were associated with NMIBC prognosis and that they improve the discriminative ability of prognostic clinical models for NMIBC. Impact: This study provides proof of concept for the joint effect of genetic variants in improving the discriminative ability of clinical prognostic models. The approach may be extended to other diseases.

Original languageEnglish (US)
Pages (from-to)1144-1150
Number of pages7
JournalCancer Epidemiology Biomarkers and Prevention
Volume25
Issue number7
DOIs
StatePublished - Jul 1 2016
Externally publishedYes

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ASJC Scopus subject areas

  • Epidemiology
  • Oncology

Cite this

Masson-Lecomte, A., De Maturana, E. L., Goddard, M. E., Picornell, A., Rava, M., González-Neira, A., Márquez, M., Carrato, A., Tardon, A., Lloreta, J., Garcia-Closas, M., Silverman, D., Rothman, N., Kogevinas, M., Allory, Y., Chanock, S. J., Real, F. X., Malats, N., Kogevinas, M., ... Mosquera, J. (2016). Inflammatory-related genetic variants in non-muscle-invasive bladder cancer prognosis: A multimarker bayesian assessment. Cancer Epidemiology Biomarkers and Prevention, 25(7), 1144-1150. https://doi.org/10.1158/1055-9965.EPI-15-0894