The variant T allele of PvuII in ESR1 gene is a prognostic marker in early breast cancer survival

Abstract The PvuII (rs2234693) Single Nucleotide Polymorphism (SNP) in the gene coding for the estrogen receptor-1 (ESR1), has been found associated with outcome in tamoxifen treated patients with early hormone-receptor positive breast cancer. However, it remains unclear whether this SNP is a predic...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Danny Houtsma, Stefanie de Groot, Renee Baak-Pablo, Elma Meershoek -Klein Kranenbarg, Caroline M. Seynaeve, Cornelis J. H. van de Velde, Stefan Böhringer, Judith R. Kroep, Henk -Jan Guchelaar, Hans Gelderblom
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7b3160633f9542b984aff99611fa5325
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:7b3160633f9542b984aff99611fa5325
record_format	dspace
spelling	oai:doaj.org-article:7b3160633f9542b984aff99611fa53252021-12-02T10:44:09ZThe variant T allele of PvuII in ESR1 gene is a prognostic marker in early breast cancer survival10.1038/s41598-021-82002-z2045-2322https://doaj.org/article/7b3160633f9542b984aff99611fa53252021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-82002-zhttps://doaj.org/toc/2045-2322Abstract The PvuII (rs2234693) Single Nucleotide Polymorphism (SNP) in the gene coding for the estrogen receptor-1 (ESR1), has been found associated with outcome in tamoxifen treated patients with early hormone-receptor positive breast cancer. However, it remains unclear whether this SNP is a predictive marker for tamoxifen efficacy or a prognostic marker for breast cancer outcome. The aim of this study was to examine the prognostic potential of this SNP in postmenopausal early breast cancer patients treated with adjuvant exemestane. Dutch postmenopausal patients randomised to 5 years of adjuvant exemestane of whom tissue was available (N = 807) were selected from the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial database. The SNP rs2234693 in the ESR1 gene was genotyped on DNA from formalin-fixed paraffin embedded (FFPE) tumor tissue using Taqman assays and related to the primary endpoint disease-free survival (DFS) and secondary endpoint overall survival (OS). Survival analyses were performed using Cox regression analysis. In total 805 patients were included in the analyses (median follow up of 5.22 years) and genotypes were obtained in 97% of the samples. The variant T allele of PvuII in ESR1 (rs2234693) was associated with a better DFS (hazard ratio (HR) 0.689, 95% confidence interval (CI) 0.480–0.989, P = 0.044) in univariate analysis only, and a better OS in both univariate (HR 0.616, 95%, CI 0.411–0.923, P = 0.019) and multivariate analyses (HR 0.571, 95% CI 0.380–0.856, P = 0.007), consistent with a prognostic rather than a predictive drug response effect. Variation of PvuII in the ESR1 gene is related to OS in postmenopausal, early HR + breast cancer patients treated with exemestane in the TEAM study. Variation in the ESR1 gene may therefore be a prognostic marker of early breast cancer survival, and warrants further research.Danny HoutsmaStefanie de GrootRenee Baak-PabloElma Meershoek -Klein KranenbargCaroline M. SeynaeveCornelis J. H. van de VeldeStefan BöhringerJudith R. KroepHenk -Jan GuchelaarHans GelderblomNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Danny Houtsma Stefanie de Groot Renee Baak-Pablo Elma Meershoek -Klein Kranenbarg Caroline M. Seynaeve Cornelis J. H. van de Velde Stefan Böhringer Judith R. Kroep Henk -Jan Guchelaar Hans Gelderblom The variant T allele of PvuII in ESR1 gene is a prognostic marker in early breast cancer survival
description	Abstract The PvuII (rs2234693) Single Nucleotide Polymorphism (SNP) in the gene coding for the estrogen receptor-1 (ESR1), has been found associated with outcome in tamoxifen treated patients with early hormone-receptor positive breast cancer. However, it remains unclear whether this SNP is a predictive marker for tamoxifen efficacy or a prognostic marker for breast cancer outcome. The aim of this study was to examine the prognostic potential of this SNP in postmenopausal early breast cancer patients treated with adjuvant exemestane. Dutch postmenopausal patients randomised to 5 years of adjuvant exemestane of whom tissue was available (N = 807) were selected from the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial database. The SNP rs2234693 in the ESR1 gene was genotyped on DNA from formalin-fixed paraffin embedded (FFPE) tumor tissue using Taqman assays and related to the primary endpoint disease-free survival (DFS) and secondary endpoint overall survival (OS). Survival analyses were performed using Cox regression analysis. In total 805 patients were included in the analyses (median follow up of 5.22 years) and genotypes were obtained in 97% of the samples. The variant T allele of PvuII in ESR1 (rs2234693) was associated with a better DFS (hazard ratio (HR) 0.689, 95% confidence interval (CI) 0.480–0.989, P = 0.044) in univariate analysis only, and a better OS in both univariate (HR 0.616, 95%, CI 0.411–0.923, P = 0.019) and multivariate analyses (HR 0.571, 95% CI 0.380–0.856, P = 0.007), consistent with a prognostic rather than a predictive drug response effect. Variation of PvuII in the ESR1 gene is related to OS in postmenopausal, early HR + breast cancer patients treated with exemestane in the TEAM study. Variation in the ESR1 gene may therefore be a prognostic marker of early breast cancer survival, and warrants further research.
format	article
author	Danny Houtsma Stefanie de Groot Renee Baak-Pablo Elma Meershoek -Klein Kranenbarg Caroline M. Seynaeve Cornelis J. H. van de Velde Stefan Böhringer Judith R. Kroep Henk -Jan Guchelaar Hans Gelderblom
author_facet	Danny Houtsma Stefanie de Groot Renee Baak-Pablo Elma Meershoek -Klein Kranenbarg Caroline M. Seynaeve Cornelis J. H. van de Velde Stefan Böhringer Judith R. Kroep Henk -Jan Guchelaar Hans Gelderblom
author_sort	Danny Houtsma
title	The variant T allele of PvuII in ESR1 gene is a prognostic marker in early breast cancer survival
title_short	The variant T allele of PvuII in ESR1 gene is a prognostic marker in early breast cancer survival
title_full	The variant T allele of PvuII in ESR1 gene is a prognostic marker in early breast cancer survival
title_fullStr	The variant T allele of PvuII in ESR1 gene is a prognostic marker in early breast cancer survival
title_full_unstemmed	The variant T allele of PvuII in ESR1 gene is a prognostic marker in early breast cancer survival
title_sort	variant t allele of pvuii in esr1 gene is a prognostic marker in early breast cancer survival
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/7b3160633f9542b984aff99611fa5325
work_keys_str_mv	AT dannyhoutsma thevarianttalleleofpvuiiinesr1geneisaprognosticmarkerinearlybreastcancersurvival AT stefaniedegroot thevarianttalleleofpvuiiinesr1geneisaprognosticmarkerinearlybreastcancersurvival AT reneebaakpablo thevarianttalleleofpvuiiinesr1geneisaprognosticmarkerinearlybreastcancersurvival AT elmameershoekkleinkranenbarg thevarianttalleleofpvuiiinesr1geneisaprognosticmarkerinearlybreastcancersurvival AT carolinemseynaeve thevarianttalleleofpvuiiinesr1geneisaprognosticmarkerinearlybreastcancersurvival AT cornelisjhvandevelde thevarianttalleleofpvuiiinesr1geneisaprognosticmarkerinearlybreastcancersurvival AT stefanbohringer thevarianttalleleofpvuiiinesr1geneisaprognosticmarkerinearlybreastcancersurvival AT judithrkroep thevarianttalleleofpvuiiinesr1geneisaprognosticmarkerinearlybreastcancersurvival AT henkjanguchelaar thevarianttalleleofpvuiiinesr1geneisaprognosticmarkerinearlybreastcancersurvival AT hansgelderblom thevarianttalleleofpvuiiinesr1geneisaprognosticmarkerinearlybreastcancersurvival AT dannyhoutsma varianttalleleofpvuiiinesr1geneisaprognosticmarkerinearlybreastcancersurvival AT stefaniedegroot varianttalleleofpvuiiinesr1geneisaprognosticmarkerinearlybreastcancersurvival AT reneebaakpablo varianttalleleofpvuiiinesr1geneisaprognosticmarkerinearlybreastcancersurvival AT elmameershoekkleinkranenbarg varianttalleleofpvuiiinesr1geneisaprognosticmarkerinearlybreastcancersurvival AT carolinemseynaeve varianttalleleofpvuiiinesr1geneisaprognosticmarkerinearlybreastcancersurvival AT cornelisjhvandevelde varianttalleleofpvuiiinesr1geneisaprognosticmarkerinearlybreastcancersurvival AT stefanbohringer varianttalleleofpvuiiinesr1geneisaprognosticmarkerinearlybreastcancersurvival AT judithrkroep varianttalleleofpvuiiinesr1geneisaprognosticmarkerinearlybreastcancersurvival AT henkjanguchelaar varianttalleleofpvuiiinesr1geneisaprognosticmarkerinearlybreastcancersurvival AT hansgelderblom varianttalleleofpvuiiinesr1geneisaprognosticmarkerinearlybreastcancersurvival
_version_	1718396835090923520

The variant T allele of PvuII in ESR1 gene is a prognostic marker in early breast cancer survival

Ejemplares similares