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...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2016-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4995039?pdf=render |
| _version_ | 1818153141613363200 |
|---|---|
| author | Jingjing Liu Anieta M Sieuwerts Maxime P Look Michelle van der Vlugt-Daane Marion E Meijer-van Gelder John A Foekens Antoinette Hollestelle John W M Martens |
| author_facet | Jingjing Liu Anieta M Sieuwerts Maxime P Look Michelle van der Vlugt-Daane Marion E Meijer-van Gelder John A Foekens Antoinette Hollestelle John W M Martens |
| author_sort | Jingjing Liu |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-11T14:05:54Z |
| format | Article |
| id | doaj.art-8434c4056c56452b90631d5cdfe90e25 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-11T14:05:54Z |
| publishDate | 2016-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-8434c4056c56452b90631d5cdfe90e252022-12-22T01:03:40ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01118e016173110.1371/journal.pone.0161731The 29.5 kb APOBEC3B Deletion Polymorphism Is Not Associated with Clinical Outcome of Breast Cancer.Jingjing LiuAnieta M SieuwertsMaxime P LookMichelle van der Vlugt-DaaneMarion E Meijer-van GelderJohn A FoekensAntoinette HollestelleJohn W M MartensIncreased 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.http://europepmc.org/articles/PMC4995039?pdf=render |
| spellingShingle | Jingjing Liu Anieta M Sieuwerts Maxime P Look Michelle van der Vlugt-Daane Marion E Meijer-van Gelder John A Foekens Antoinette Hollestelle John W M Martens The 29.5 kb APOBEC3B Deletion Polymorphism Is Not Associated with Clinical Outcome of Breast Cancer. PLoS ONE |
| 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 |
| url | http://europepmc.org/articles/PMC4995039?pdf=render |
| work_keys_str_mv | AT jingjingliu the295kbapobec3bdeletionpolymorphismisnotassociatedwithclinicaloutcomeofbreastcancer AT anietamsieuwerts the295kbapobec3bdeletionpolymorphismisnotassociatedwithclinicaloutcomeofbreastcancer AT maximeplook the295kbapobec3bdeletionpolymorphismisnotassociatedwithclinicaloutcomeofbreastcancer AT michellevandervlugtdaane the295kbapobec3bdeletionpolymorphismisnotassociatedwithclinicaloutcomeofbreastcancer AT marionemeijervangelder the295kbapobec3bdeletionpolymorphismisnotassociatedwithclinicaloutcomeofbreastcancer AT johnafoekens the295kbapobec3bdeletionpolymorphismisnotassociatedwithclinicaloutcomeofbreastcancer AT antoinettehollestelle the295kbapobec3bdeletionpolymorphismisnotassociatedwithclinicaloutcomeofbreastcancer AT johnwmmartens the295kbapobec3bdeletionpolymorphismisnotassociatedwithclinicaloutcomeofbreastcancer AT jingjingliu 295kbapobec3bdeletionpolymorphismisnotassociatedwithclinicaloutcomeofbreastcancer AT anietamsieuwerts 295kbapobec3bdeletionpolymorphismisnotassociatedwithclinicaloutcomeofbreastcancer AT maximeplook 295kbapobec3bdeletionpolymorphismisnotassociatedwithclinicaloutcomeofbreastcancer AT michellevandervlugtdaane 295kbapobec3bdeletionpolymorphismisnotassociatedwithclinicaloutcomeofbreastcancer AT marionemeijervangelder 295kbapobec3bdeletionpolymorphismisnotassociatedwithclinicaloutcomeofbreastcancer AT johnafoekens 295kbapobec3bdeletionpolymorphismisnotassociatedwithclinicaloutcomeofbreastcancer AT antoinettehollestelle 295kbapobec3bdeletionpolymorphismisnotassociatedwithclinicaloutcomeofbreastcancer AT johnwmmartens 295kbapobec3bdeletionpolymorphismisnotassociatedwithclinicaloutcomeofbreastcancer |