Cargando…

The 29.5 kb APOBEC3B Deletion Polymorphism Is Not Associated with Clinical Outcome of Breast Cancer

Increased APOBEC3B mRNA levels are associated with a hypermutator phenotype and poor prognosis in ER-positive breast cancer patients. In addition, a 29.5 kb deletion polymorphism of APOBEC3B, resulting in an APOBEC3A-B hybrid transcript, has been associated with an increased breast cancer risk and t...

Descripción completa

Detalles Bibliográficos
Autores principales: Liu, Jingjing, Sieuwerts, Anieta M., Look, Maxime P., van der Vlugt-Daane, Michelle, Meijer-van Gelder, Marion E., Foekens, John A., Hollestelle, Antoinette, Martens, John W. M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4995039/
https://www.ncbi.nlm.nih.gov/pubmed/27552096
http://dx.doi.org/10.1371/journal.pone.0161731
_version_ 1782449409068367872
author Liu, Jingjing
Sieuwerts, Anieta M.
Look, Maxime P.
van der Vlugt-Daane, Michelle
Meijer-van Gelder, Marion E.
Foekens, John A.
Hollestelle, Antoinette
Martens, John W. M.
author_facet Liu, Jingjing
Sieuwerts, Anieta M.
Look, Maxime P.
van der Vlugt-Daane, Michelle
Meijer-van Gelder, Marion E.
Foekens, John A.
Hollestelle, Antoinette
Martens, John W. M.
author_sort Liu, Jingjing
collection PubMed
description Increased APOBEC3B mRNA levels are associated with a hypermutator phenotype and poor prognosis in ER-positive breast cancer patients. In addition, a 29.5 kb deletion polymorphism of APOBEC3B, resulting in an APOBEC3A-B hybrid transcript, has been associated with an increased breast cancer risk and the hypermutator phenotype. Here we evaluated whether the APOBEC3B deletion polymorphism also associates with clinical outcome of breast cancer. Copy number analysis was performed by quantitative PCR (qPCR) in primary tumors of 1,756 Dutch breast cancer patients. The APOBEC3B deletion was found in 187 patients of whom 16 carried a two-copy deletion and 171 carried a one-copy deletion. The prognostic value of the APOBEC3B deletion for the natural course of the disease was evaluated among 1,076 lymph-node negative (LNN) patients who did not receive adjuvant systemic treatment. No association was found between APOBEC3B copy number values and the length of metastasis-free survival (MFS; hazard ratio (HR) = 1.00, 95% confidence interval (CI) = 0.90–1.11, P = 0.96). Subgroup analysis by ER status also did not reveal an association between APOBEC3B copy number values and the length of MFS. The predictive value of the APOBEC3B deletion was assessed among 329 ER-positive breast cancer patients who received tamoxifen as the first-line therapy for recurrent disease and 226 breast cancer patients who received first-line chemotherapy for recurrent disease. No association between APOBEC3B copy number values and the overall response rate (ORR) to either tamoxifen (odds ratio (OR) = 0.88, 95% CI = 0.69–1.13, P = 0.31) or chemotherapy (OR = 0.97, 95% CI = 0.71–1.33, P = 0.87) was found. Thus, in contrast to APOBEC3B mRNA levels, the APOBEC3B deletion polymorphism has neither a prognostic nor a predictive value for breast cancer patients. Although a correlation exists between APOBEC3B copy number and mRNA expression, it is relatively weak. This suggests that other mechanisms exist that may affect and therefore determine the prognostic value of APOBEC3B mRNA levels.
format Online
Article
Text
id pubmed-4995039
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-49950392016-09-12 The 29.5 kb APOBEC3B Deletion Polymorphism Is Not Associated with Clinical Outcome of Breast Cancer Liu, Jingjing Sieuwerts, Anieta M. Look, Maxime P. van der Vlugt-Daane, Michelle Meijer-van Gelder, Marion E. Foekens, John A. Hollestelle, Antoinette Martens, John W. M. PLoS One Research Article Increased APOBEC3B mRNA levels are associated with a hypermutator phenotype and poor prognosis in ER-positive breast cancer patients. In addition, a 29.5 kb deletion polymorphism of APOBEC3B, resulting in an APOBEC3A-B hybrid transcript, has been associated with an increased breast cancer risk and the hypermutator phenotype. Here we evaluated whether the APOBEC3B deletion polymorphism also associates with clinical outcome of breast cancer. Copy number analysis was performed by quantitative PCR (qPCR) in primary tumors of 1,756 Dutch breast cancer patients. The APOBEC3B deletion was found in 187 patients of whom 16 carried a two-copy deletion and 171 carried a one-copy deletion. The prognostic value of the APOBEC3B deletion for the natural course of the disease was evaluated among 1,076 lymph-node negative (LNN) patients who did not receive adjuvant systemic treatment. No association was found between APOBEC3B copy number values and the length of metastasis-free survival (MFS; hazard ratio (HR) = 1.00, 95% confidence interval (CI) = 0.90–1.11, P = 0.96). Subgroup analysis by ER status also did not reveal an association between APOBEC3B copy number values and the length of MFS. The predictive value of the APOBEC3B deletion was assessed among 329 ER-positive breast cancer patients who received tamoxifen as the first-line therapy for recurrent disease and 226 breast cancer patients who received first-line chemotherapy for recurrent disease. No association between APOBEC3B copy number values and the overall response rate (ORR) to either tamoxifen (odds ratio (OR) = 0.88, 95% CI = 0.69–1.13, P = 0.31) or chemotherapy (OR = 0.97, 95% CI = 0.71–1.33, P = 0.87) was found. Thus, in contrast to APOBEC3B mRNA levels, the APOBEC3B deletion polymorphism has neither a prognostic nor a predictive value for breast cancer patients. Although a correlation exists between APOBEC3B copy number and mRNA expression, it is relatively weak. This suggests that other mechanisms exist that may affect and therefore determine the prognostic value of APOBEC3B mRNA levels. Public Library of Science 2016-08-23 /pmc/articles/PMC4995039/ /pubmed/27552096 http://dx.doi.org/10.1371/journal.pone.0161731 Text en © 2016 Liu et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Liu, Jingjing
Sieuwerts, Anieta M.
Look, Maxime P.
van der Vlugt-Daane, Michelle
Meijer-van Gelder, Marion E.
Foekens, John A.
Hollestelle, Antoinette
Martens, John W. M.
The 29.5 kb APOBEC3B Deletion Polymorphism Is Not Associated with Clinical Outcome of Breast Cancer
title The 29.5 kb APOBEC3B Deletion Polymorphism Is Not Associated with Clinical Outcome of Breast Cancer
title_full The 29.5 kb APOBEC3B Deletion Polymorphism Is Not Associated with Clinical Outcome of Breast Cancer
title_fullStr The 29.5 kb APOBEC3B Deletion Polymorphism Is Not Associated with Clinical Outcome of Breast Cancer
title_full_unstemmed The 29.5 kb APOBEC3B Deletion Polymorphism Is Not Associated with Clinical Outcome of Breast Cancer
title_short The 29.5 kb APOBEC3B Deletion Polymorphism Is Not Associated with Clinical Outcome of Breast Cancer
title_sort 29.5 kb apobec3b deletion polymorphism is not associated with clinical outcome of breast cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4995039/
https://www.ncbi.nlm.nih.gov/pubmed/27552096
http://dx.doi.org/10.1371/journal.pone.0161731
work_keys_str_mv AT liujingjing the295kbapobec3bdeletionpolymorphismisnotassociatedwithclinicaloutcomeofbreastcancer
AT sieuwertsanietam the295kbapobec3bdeletionpolymorphismisnotassociatedwithclinicaloutcomeofbreastcancer
AT lookmaximep the295kbapobec3bdeletionpolymorphismisnotassociatedwithclinicaloutcomeofbreastcancer
AT vandervlugtdaanemichelle the295kbapobec3bdeletionpolymorphismisnotassociatedwithclinicaloutcomeofbreastcancer
AT meijervangeldermarione the295kbapobec3bdeletionpolymorphismisnotassociatedwithclinicaloutcomeofbreastcancer
AT foekensjohna the295kbapobec3bdeletionpolymorphismisnotassociatedwithclinicaloutcomeofbreastcancer
AT hollestelleantoinette the295kbapobec3bdeletionpolymorphismisnotassociatedwithclinicaloutcomeofbreastcancer
AT martensjohnwm the295kbapobec3bdeletionpolymorphismisnotassociatedwithclinicaloutcomeofbreastcancer
AT liujingjing 295kbapobec3bdeletionpolymorphismisnotassociatedwithclinicaloutcomeofbreastcancer
AT sieuwertsanietam 295kbapobec3bdeletionpolymorphismisnotassociatedwithclinicaloutcomeofbreastcancer
AT lookmaximep 295kbapobec3bdeletionpolymorphismisnotassociatedwithclinicaloutcomeofbreastcancer
AT vandervlugtdaanemichelle 295kbapobec3bdeletionpolymorphismisnotassociatedwithclinicaloutcomeofbreastcancer
AT meijervangeldermarione 295kbapobec3bdeletionpolymorphismisnotassociatedwithclinicaloutcomeofbreastcancer
AT foekensjohna 295kbapobec3bdeletionpolymorphismisnotassociatedwithclinicaloutcomeofbreastcancer
AT hollestelleantoinette 295kbapobec3bdeletionpolymorphismisnotassociatedwithclinicaloutcomeofbreastcancer
AT martensjohnwm 295kbapobec3bdeletionpolymorphismisnotassociatedwithclinicaloutcomeofbreastcancer