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. Malats & 74 others F. 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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Urinary Bladder Neoplasms
Single Nucleotide Polymorphism
Recurrence
Genes

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., ... 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

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

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 25, No. 7, 01.07.2016, p. 1144-1150.

Research output: Contribution to journalArticle

Masson-Lecomte, A, De Maturana, EL, Goddard, ME, 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, SJ, Real, FX, Malats, N, Kogevinas, M, Malats, N, Real, FX, Sala, M, Castano, G, Tora, M, Puente, D, Villanueva, C, Murta-Nascimento, C, Fortuny, J, Lopez, E, Hernandez, S, Jaramillo, R, Vellalta, G, Palencia, L, Fermandez, F, Amoros, A, Alfaro, A, Carretero, G, Lloreta, J, Serrano, S, Ferrer, L, Gelabert, A, Carles, J, Bielsa, O, Villadiego, K, Cecchini, L, Saladie, JM, Ibarz, L, Cespedes, M, Serra, C, García, D, Pujadas, J, Hernando, R, Cabezuelo, A, Abad, C, Prera, A, Prat, J, Domenech, M, Badal, J, Malet, J, García-Closas, R, Rodríguez De Vera, J, Martín, AI, Tano, J, Caceres, F, Carrato, A, García-Lopez, F, Ull, M, Teruel, A, Andrada, E, Bustos, A, Castillejo, A, Soto, JL, Tardon, A, Guate, JL, Lanzas, JM, Velasco, J, Fernandez, JM, Rodríguez, JJ, Herrero, A, Abascal, R, Manzano, C, Miralles, T, Rivas, M, Arguelles, M, Díaz, M, Sanchez, J, Gonzalez, O, Mateos, A, Frade, V, Muntanola, P, Pravia, C, Huescar, AM, Huergo, F & Mosquera, J 2016, 'Inflammatory-related genetic variants in non-muscle-invasive bladder cancer prognosis: A multimarker bayesian assessment', Cancer Epidemiology Biomarkers and Prevention, vol. 25, no. 7, pp. 1144-1150. https://doi.org/10.1158/1055-9965.EPI-15-0894
Masson-Lecomte, Alexandra ; De Maturana, Evangelina López ; Goddard, Michael E. ; Picornell, Antoni ; Rava, Marta ; González-Neira, Anna ; Márquez, Mirari ; Carrato, Alfredo ; Tardon, Adonina ; Lloreta, Josep ; Garcia-Closas, Montserrat ; Silverman, Debra ; Rothman, Nathaniel ; Kogevinas, Manolis ; Allory, Yves ; Chanock, Stephen J. ; Real, Francisco X. ; Malats, Núria ; Kogevinas, M. ; Malats, N. ; Real, F. X. ; Sala, M. ; Castano, G. ; Tora, M. ; Puente, D. ; Villanueva, C. ; Murta-Nascimento, C. ; Fortuny, J. ; Lopez, E. ; Hernandez, S. ; Jaramillo, R. ; Vellalta, G. ; Palencia, L. ; Fermandez, F. ; Amoros, A. ; Alfaro, A. ; Carretero, G. ; Lloreta, J. ; Serrano, S. ; Ferrer, L. ; Gelabert, A. ; Carles, J. ; Bielsa, O. ; Villadiego, K. ; Cecchini, L. ; Saladie, J. M. ; Ibarz, L. ; Cespedes, M. ; Serra, C. ; García, D. ; Pujadas, J. ; Hernando, R. ; Cabezuelo, A. ; Abad, C. ; Prera, A. ; Prat, J. ; Domenech, M. ; Badal, J. ; Malet, J. ; García-Closas, R. ; Rodríguez De Vera, J. ; Martín, A. I. ; Tano, J. ; Caceres, F. ; Carrato, A. ; García-Lopez, F. ; Ull, M. ; Teruel, A. ; Andrada, E. ; Bustos, A. ; Castillejo, A. ; Soto, J. L. ; Tardon, A. ; Guate, J. L. ; Lanzas, J. M. ; Velasco, J. ; Fernandez, J. M. ; Rodríguez, J. J. ; Herrero, A. ; Abascal, R. ; Manzano, C. ; Miralles, T. ; Rivas, M. ; Arguelles, M. ; Díaz, M. ; Sanchez, J. ; Gonzalez, O. ; Mateos, A. ; Frade, V. ; Muntanola, P. ; Pravia, C. ; Huescar, A. M. ; Huergo, F. ; Mosquera, J. / Inflammatory-related genetic variants in non-muscle-invasive bladder cancer prognosis : A multimarker bayesian assessment. In: Cancer Epidemiology Biomarkers and Prevention. 2016 ; Vol. 25, No. 7. pp. 1144-1150.
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title = "Inflammatory-related genetic variants in non-muscle-invasive bladder cancer prognosis: A multimarker bayesian assessment",
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.",
author = "Alexandra Masson-Lecomte and {De Maturana}, {Evangelina L{\'o}pez} and Goddard, {Michael E.} and Antoni Picornell and Marta Rava and Anna Gonz{\'a}lez-Neira and Mirari M{\'a}rquez and Alfredo Carrato and Adonina Tardon and Josep Lloreta and Montserrat Garcia-Closas and Debra Silverman and Nathaniel Rothman and Manolis Kogevinas and Yves Allory and Chanock, {Stephen J.} and Real, {Francisco X.} and N{\'u}ria Malats and M. Kogevinas and N. Malats and Real, {F. X.} and M. Sala and G. Castano and M. Tora and D. Puente and C. Villanueva and C. Murta-Nascimento and J. Fortuny and E. Lopez and S. Hernandez and R. Jaramillo and G. Vellalta and L. Palencia and F. Fermandez and A. Amoros and A. Alfaro and G. Carretero and J. Lloreta and S. Serrano and L. Ferrer and A. Gelabert and J. Carles and O. Bielsa and K. Villadiego and L. Cecchini and Saladie, {J. M.} and L. Ibarz and M. Cespedes and C. Serra and D. Garc{\'i}a and J. Pujadas and R. Hernando and A. Cabezuelo and C. Abad and A. Prera and J. Prat and M. Domenech and J. Badal and J. Malet and R. Garc{\'i}a-Closas and {Rodr{\'i}guez De Vera}, J. and Mart{\'i}n, {A. I.} and J. Tano and F. Caceres and A. Carrato and F. Garc{\'i}a-Lopez and M. Ull and A. Teruel and E. Andrada and A. Bustos and A. Castillejo and Soto, {J. L.} and A. Tardon and Guate, {J. L.} and Lanzas, {J. M.} and J. Velasco and Fernandez, {J. M.} and Rodr{\'i}guez, {J. J.} and A. Herrero and R. Abascal and C. Manzano and T. Miralles and M. Rivas and M. Arguelles and M. D{\'i}az and J. Sanchez and O. Gonzalez and A. Mateos and V. Frade and P. Muntanola and C. Pravia and Huescar, {A. M.} and F. Huergo and J. Mosquera",
year = "2016",
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doi = "10.1158/1055-9965.EPI-15-0894",
language = "English (US)",
volume = "25",
pages = "1144--1150",
journal = "Cancer Epidemiology Biomarkers and Prevention",
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TY - JOUR

T1 - Inflammatory-related genetic variants in non-muscle-invasive bladder cancer prognosis

T2 - A multimarker bayesian assessment

AU - Masson-Lecomte, Alexandra

AU - De Maturana, Evangelina López

AU - Goddard, Michael E.

AU - Picornell, Antoni

AU - Rava, Marta

AU - González-Neira, Anna

AU - Márquez, Mirari

AU - Carrato, Alfredo

AU - Tardon, Adonina

AU - Lloreta, Josep

AU - Garcia-Closas, Montserrat

AU - Silverman, Debra

AU - Rothman, Nathaniel

AU - Kogevinas, Manolis

AU - Allory, Yves

AU - Chanock, Stephen J.

AU - Real, Francisco X.

AU - Malats, Núria

AU - Kogevinas, M.

AU - Malats, N.

AU - Real, F. X.

AU - Sala, M.

AU - Castano, G.

AU - Tora, M.

AU - Puente, D.

AU - Villanueva, C.

AU - Murta-Nascimento, C.

AU - Fortuny, J.

AU - Lopez, E.

AU - Hernandez, S.

AU - Jaramillo, R.

AU - Vellalta, G.

AU - Palencia, L.

AU - Fermandez, F.

AU - Amoros, A.

AU - Alfaro, A.

AU - Carretero, G.

AU - Lloreta, J.

AU - Serrano, S.

AU - Ferrer, L.

AU - Gelabert, A.

AU - Carles, J.

AU - Bielsa, O.

AU - Villadiego, K.

AU - Cecchini, L.

AU - Saladie, J. M.

AU - Ibarz, L.

AU - Cespedes, M.

AU - Serra, C.

AU - García, D.

AU - Pujadas, J.

AU - Hernando, R.

AU - Cabezuelo, A.

AU - Abad, C.

AU - Prera, A.

AU - Prat, J.

AU - Domenech, M.

AU - Badal, J.

AU - Malet, J.

AU - García-Closas, R.

AU - Rodríguez De Vera, J.

AU - Martín, A. I.

AU - Tano, J.

AU - Caceres, F.

AU - Carrato, A.

AU - García-Lopez, F.

AU - Ull, M.

AU - Teruel, A.

AU - Andrada, E.

AU - Bustos, A.

AU - Castillejo, A.

AU - Soto, J. L.

AU - Tardon, A.

AU - Guate, J. L.

AU - Lanzas, J. M.

AU - Velasco, J.

AU - Fernandez, J. M.

AU - Rodríguez, J. J.

AU - Herrero, A.

AU - Abascal, R.

AU - Manzano, C.

AU - Miralles, T.

AU - Rivas, M.

AU - Arguelles, M.

AU - Díaz, M.

AU - Sanchez, J.

AU - Gonzalez, O.

AU - Mateos, A.

AU - Frade, V.

AU - Muntanola, P.

AU - Pravia, C.

AU - Huescar, A. M.

AU - Huergo, F.

AU - Mosquera, J.

PY - 2016/7/1

Y1 - 2016/7/1

N2 - 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.

AB - 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.

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UR - http://www.scopus.com/inward/citedby.url?scp=84977106953&partnerID=8YFLogxK

U2 - 10.1158/1055-9965.EPI-15-0894

DO - 10.1158/1055-9965.EPI-15-0894

M3 - Article

VL - 25

SP - 1144

EP - 1150

JO - Cancer Epidemiology Biomarkers and Prevention

JF - Cancer Epidemiology Biomarkers and Prevention

SN - 1055-9965

IS - 7

ER -