Glutathione-S-transferase (GST) polymorphisms are associated with relapse after radical prostatectomy

Autores
Cotignola, Javier Hernan; Leonardi, Daiana Beatriz; Shahabi, A.; Acuña, Alejandro Daniel; Stern, M. C.; Navone, N.; Scorticati, C.; de Siervi, Adriana; Mazza, O.; Vazquez, Elba Susana
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
BACKGROUND: Organ confined prostate cancer (PCa) can be cured by radical retropubic prostatectomy (RRP); however, some tumors will still recur. Current tools fail to identify patients at risk of recurrence. Glutathione-S-transferases (GSTs) are involved in the metabolism of carcinogens, hormones and drugs. Thus, genetic polymorphisms that modify the GST activities may modify the risk of PCa recurrence. METHODS: We retrospectively recruited Argentine PCa patients treated with RRP to study the association between GST polymorphisms and PCa biochemical relapse after RRP. We genotyped germline DNA in 105 patients for: GSTP1 c.313A4G (p.105 Ile4Val, rs1695) by PCR-RFLP; and GSTT1 null and GSTM1 null polymorphisms by multiplex PCR. Kaplan–Meier curves and Cox proportional hazard models were used to evaluate these associations. RESULTS: Patients with GSTP1 c.313GG genotype showed shorter biochemical relapse-free survival (BRFS) (P ¼ 0.003) and higher risk for recurrence in unadjusted (Hazard ratio (HR) ¼ 3.16, 95% confidence interval (95% CI) ¼ 1.41–7.06, P ¼ 0.005) and multivariate models (HR ¼ 3.01, 95% CI ¼ 1.13–8.02, P ¼ 0.028). We did not find significant associations for GSTT1 and GSTM1 genotypes. In addition, we found shorter BRFS (P ¼ 0.010) and increased risk for recurrence for patients having two or more risk alleles when we combined the genotypes of the three GSTs in multivariate models (HR ¼ 3.06, 95% CI ¼ 1.20–7.80, P ¼ 0.019). CONCLUSIONS: Our results give support to the implementation of GSTs genotyping for personalized therapies as a novel alternative for PCa management for patients who undergo RRP. To the best of our knowledge, this is the first study that examined GST polymorphisms in PCa progression in Argentine men. Replication of our findings in larger cohort is warranted.
Fil: Cotignola, Javier Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Leonardi, Daiana Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Shahabi, A.. University Of Southern California; Estados Unidos
Fil: Acuña, Alejandro Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Stern, M. C.. University Of Southern California; Estados Unidos
Fil: Navone, N.. University of Texas; Estados Unidos
Fil: Scorticati, C.. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina
Fil: de Siervi, Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Mazza, O.. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina
Fil: Vazquez, Elba Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Materia
Prostate Cancer
Biochemical Relapse
Gst
Glutathione-S-Transerase
Polymorphism
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/21235
Acceder
id CONICETDig_d8046151ef31251f9e9b3161a33f0e2f
oai_identifier_str oai:ri.conicet.gov.ar:11336/21235
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Glutathione-S-transferase (GST) polymorphisms are associated with relapse after radical prostatectomyCotignola, Javier HernanLeonardi, Daiana BeatrizShahabi, A.Acuña, Alejandro DanielStern, M. C.Navone, N.Scorticati, C.de Siervi, AdrianaMazza, O.Vazquez, Elba SusanaProstate CancerBiochemical RelapseGstGlutathione-S-TranserasePolymorphismhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1BACKGROUND: Organ confined prostate cancer (PCa) can be cured by radical retropubic prostatectomy (RRP); however, some tumors will still recur. Current tools fail to identify patients at risk of recurrence. Glutathione-S-transferases (GSTs) are involved in the metabolism of carcinogens, hormones and drugs. Thus, genetic polymorphisms that modify the GST activities may modify the risk of PCa recurrence. METHODS: We retrospectively recruited Argentine PCa patients treated with RRP to study the association between GST polymorphisms and PCa biochemical relapse after RRP. We genotyped germline DNA in 105 patients for: GSTP1 c.313A4G (p.105 Ile4Val, rs1695) by PCR-RFLP; and GSTT1 null and GSTM1 null polymorphisms by multiplex PCR. Kaplan–Meier curves and Cox proportional hazard models were used to evaluate these associations. RESULTS: Patients with GSTP1 c.313GG genotype showed shorter biochemical relapse-free survival (BRFS) (P ¼ 0.003) and higher risk for recurrence in unadjusted (Hazard ratio (HR) ¼ 3.16, 95% confidence interval (95% CI) ¼ 1.41–7.06, P ¼ 0.005) and multivariate models (HR ¼ 3.01, 95% CI ¼ 1.13–8.02, P ¼ 0.028). We did not find significant associations for GSTT1 and GSTM1 genotypes. In addition, we found shorter BRFS (P ¼ 0.010) and increased risk for recurrence for patients having two or more risk alleles when we combined the genotypes of the three GSTs in multivariate models (HR ¼ 3.06, 95% CI ¼ 1.20–7.80, P ¼ 0.019). CONCLUSIONS: Our results give support to the implementation of GSTs genotyping for personalized therapies as a novel alternative for PCa management for patients who undergo RRP. To the best of our knowledge, this is the first study that examined GST polymorphisms in PCa progression in Argentine men. Replication of our findings in larger cohort is warranted.Fil: Cotignola, Javier Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Leonardi, Daiana Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Shahabi, A.. University Of Southern California; Estados UnidosFil: Acuña, Alejandro Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Stern, M. C.. University Of Southern California; Estados UnidosFil: Navone, N.. University of Texas; Estados UnidosFil: Scorticati, C.. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: de Siervi, Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Mazza, O.. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Vazquez, Elba Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaNature Publishing Group2013-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/21235Cotignola, Javier Hernan; Leonardi, Daiana Beatriz; Shahabi, A.; Acuña, Alejandro Daniel; Stern, M. C.; et al.; Glutathione-S-transferase (GST) polymorphisms are associated with relapse after radical prostatectomy; Nature Publishing Group; Prostate Cancer And Prostatic Diseases; 16; 3-2013; 28-341365-7852CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1038/pcan.2012.45info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/pcan/journal/v16/n1/full/pcan201245a.htmlinfo:eu-repo/semantics/altIdentifier/url/https://pubmed.ncbi.nlm.nih.gov/23146971/info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:05:29Zoai:ri.conicet.gov.ar:11336/21235instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-10 13:05:29.689CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Glutathione-S-transferase (GST) polymorphisms are associated with relapse after radical prostatectomy
title Glutathione-S-transferase (GST) polymorphisms are associated with relapse after radical prostatectomy
spellingShingle Glutathione-S-transferase (GST) polymorphisms are associated with relapse after radical prostatectomy
Cotignola, Javier Hernan
Prostate Cancer
Biochemical Relapse
Gst
Glutathione-S-Transerase
Polymorphism
title_short Glutathione-S-transferase (GST) polymorphisms are associated with relapse after radical prostatectomy
title_full Glutathione-S-transferase (GST) polymorphisms are associated with relapse after radical prostatectomy
title_fullStr Glutathione-S-transferase (GST) polymorphisms are associated with relapse after radical prostatectomy
title_full_unstemmed Glutathione-S-transferase (GST) polymorphisms are associated with relapse after radical prostatectomy
title_sort Glutathione-S-transferase (GST) polymorphisms are associated with relapse after radical prostatectomy
dc.creator.none.fl_str_mv Cotignola, Javier Hernan
Leonardi, Daiana Beatriz
Shahabi, A.
Acuña, Alejandro Daniel
Stern, M. C.
Navone, N.
Scorticati, C.
de Siervi, Adriana
Mazza, O.
Vazquez, Elba Susana
author Cotignola, Javier Hernan
author_facet Cotignola, Javier Hernan
Leonardi, Daiana Beatriz
Shahabi, A.
Acuña, Alejandro Daniel
Stern, M. C.
Navone, N.
Scorticati, C.
de Siervi, Adriana
Mazza, O.
Vazquez, Elba Susana
author_role author
author2 Leonardi, Daiana Beatriz
Shahabi, A.
Acuña, Alejandro Daniel
Stern, M. C.
Navone, N.
Scorticati, C.
de Siervi, Adriana
Mazza, O.
Vazquez, Elba Susana
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Prostate Cancer
Biochemical Relapse
Gst
Glutathione-S-Transerase
Polymorphism
topic Prostate Cancer
Biochemical Relapse
Gst
Glutathione-S-Transerase
Polymorphism
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv BACKGROUND: Organ confined prostate cancer (PCa) can be cured by radical retropubic prostatectomy (RRP); however, some tumors will still recur. Current tools fail to identify patients at risk of recurrence. Glutathione-S-transferases (GSTs) are involved in the metabolism of carcinogens, hormones and drugs. Thus, genetic polymorphisms that modify the GST activities may modify the risk of PCa recurrence. METHODS: We retrospectively recruited Argentine PCa patients treated with RRP to study the association between GST polymorphisms and PCa biochemical relapse after RRP. We genotyped germline DNA in 105 patients for: GSTP1 c.313A4G (p.105 Ile4Val, rs1695) by PCR-RFLP; and GSTT1 null and GSTM1 null polymorphisms by multiplex PCR. Kaplan–Meier curves and Cox proportional hazard models were used to evaluate these associations. RESULTS: Patients with GSTP1 c.313GG genotype showed shorter biochemical relapse-free survival (BRFS) (P ¼ 0.003) and higher risk for recurrence in unadjusted (Hazard ratio (HR) ¼ 3.16, 95% confidence interval (95% CI) ¼ 1.41–7.06, P ¼ 0.005) and multivariate models (HR ¼ 3.01, 95% CI ¼ 1.13–8.02, P ¼ 0.028). We did not find significant associations for GSTT1 and GSTM1 genotypes. In addition, we found shorter BRFS (P ¼ 0.010) and increased risk for recurrence for patients having two or more risk alleles when we combined the genotypes of the three GSTs in multivariate models (HR ¼ 3.06, 95% CI ¼ 1.20–7.80, P ¼ 0.019). CONCLUSIONS: Our results give support to the implementation of GSTs genotyping for personalized therapies as a novel alternative for PCa management for patients who undergo RRP. To the best of our knowledge, this is the first study that examined GST polymorphisms in PCa progression in Argentine men. Replication of our findings in larger cohort is warranted.
Fil: Cotignola, Javier Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Leonardi, Daiana Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Shahabi, A.. University Of Southern California; Estados Unidos
Fil: Acuña, Alejandro Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Stern, M. C.. University Of Southern California; Estados Unidos
Fil: Navone, N.. University of Texas; Estados Unidos
Fil: Scorticati, C.. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina
Fil: de Siervi, Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Mazza, O.. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina
Fil: Vazquez, Elba Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
description BACKGROUND: Organ confined prostate cancer (PCa) can be cured by radical retropubic prostatectomy (RRP); however, some tumors will still recur. Current tools fail to identify patients at risk of recurrence. Glutathione-S-transferases (GSTs) are involved in the metabolism of carcinogens, hormones and drugs. Thus, genetic polymorphisms that modify the GST activities may modify the risk of PCa recurrence. METHODS: We retrospectively recruited Argentine PCa patients treated with RRP to study the association between GST polymorphisms and PCa biochemical relapse after RRP. We genotyped germline DNA in 105 patients for: GSTP1 c.313A4G (p.105 Ile4Val, rs1695) by PCR-RFLP; and GSTT1 null and GSTM1 null polymorphisms by multiplex PCR. Kaplan–Meier curves and Cox proportional hazard models were used to evaluate these associations. RESULTS: Patients with GSTP1 c.313GG genotype showed shorter biochemical relapse-free survival (BRFS) (P ¼ 0.003) and higher risk for recurrence in unadjusted (Hazard ratio (HR) ¼ 3.16, 95% confidence interval (95% CI) ¼ 1.41–7.06, P ¼ 0.005) and multivariate models (HR ¼ 3.01, 95% CI ¼ 1.13–8.02, P ¼ 0.028). We did not find significant associations for GSTT1 and GSTM1 genotypes. In addition, we found shorter BRFS (P ¼ 0.010) and increased risk for recurrence for patients having two or more risk alleles when we combined the genotypes of the three GSTs in multivariate models (HR ¼ 3.06, 95% CI ¼ 1.20–7.80, P ¼ 0.019). CONCLUSIONS: Our results give support to the implementation of GSTs genotyping for personalized therapies as a novel alternative for PCa management for patients who undergo RRP. To the best of our knowledge, this is the first study that examined GST polymorphisms in PCa progression in Argentine men. Replication of our findings in larger cohort is warranted.
publishDate 2013
dc.date.none.fl_str_mv 2013-03
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/21235
Cotignola, Javier Hernan; Leonardi, Daiana Beatriz; Shahabi, A.; Acuña, Alejandro Daniel; Stern, M. C.; et al.; Glutathione-S-transferase (GST) polymorphisms are associated with relapse after radical prostatectomy; Nature Publishing Group; Prostate Cancer And Prostatic Diseases; 16; 3-2013; 28-34
1365-7852
CONICET Digital
CONICET
url http://hdl.handle.net/11336/21235
identifier_str_mv Cotignola, Javier Hernan; Leonardi, Daiana Beatriz; Shahabi, A.; Acuña, Alejandro Daniel; Stern, M. C.; et al.; Glutathione-S-transferase (GST) polymorphisms are associated with relapse after radical prostatectomy; Nature Publishing Group; Prostate Cancer And Prostatic Diseases; 16; 3-2013; 28-34
1365-7852
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
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info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/pcan/journal/v16/n1/full/pcan201245a.html
info:eu-repo/semantics/altIdentifier/url/https://pubmed.ncbi.nlm.nih.gov/23146971/
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
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dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
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repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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