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A genome-wide association study identifies three novel genetic markers for response to tamoxifen: A prospective multicenter study.
- Source :
-
PloS one [PLoS One] 2018 Aug 30; Vol. 13 (8), pp. e0201606. Date of Electronic Publication: 2018 Aug 30 (Print Publication: 2018). - Publication Year :
- 2018
-
Abstract
- Purpose: Although association studies of genetic variations with the clinical outcomes of breast cancer patients treated with tamoxifen have been reported, genetic factors which could determine individual response to tamoxifen are not fully clarified. We performed a genome-wide association study (GWAS) to identify novel genetic markers for response to tamoxifen.<br />Experimental Design: We prospectively collected 347 blood samples from patients with hormone receptor-positive and human epidermal growth factor receptor 2-negative, invasive breast cancer receiving preoperative tamoxifen monotherapy for 14 to 28 days. We used Ki-67 response in breast cancer tissues after preoperative short-term tamoxifen therapy as a surrogate marker for response to tamoxifen. We performed GWAS and genotype imputation using 275 patients, and an independent set of 72 patients was used for replication study.<br />Results: The combined result of GWAS and the replication study, and subsequent imputation analysis indicated possible association of three loci with Ki-67 response after tamoxifen therapy (rs17198973 on chromosome 4q34.3, rs4577773 on 6q12, and rs7087428 on 10p13, Pcombined = 5.69 x 10-6, 1.64 x 10-5, and 9.77 x 10-6, respectively). When patients were classified into three groups by the scoring system based on the genotypes of the three SNPs, patients with higher scores showed significantly higher after/before ratio of Ki-67 compared to those with lower scores (P = 1.8 x 10-12), suggesting the cumulative effect of the three SNPs.<br />Conclusion: We identified three novel loci, which could be associated with clinical response to tamoxifen. These findings provide new insights into personalized hormonal therapy for the patients with breast cancer.<br />Competing Interests: The authors have declared that no competing interests exist.
- Subjects :
- Adult
Aged
Aged, 80 and over
Breast Neoplasms genetics
Breast Neoplasms metabolism
Breast Neoplasms surgery
Chromosomes, Human genetics
Female
Humans
Ki-67 Antigen metabolism
Middle Aged
Preoperative Care
Prospective Studies
Receptor, ErbB-2 metabolism
Sequence Analysis, DNA
Tamoxifen pharmacology
Treatment Outcome
Breast Neoplasms drug therapy
Genetic Markers drug effects
Genome-Wide Association Study methods
Polymorphism, Single Nucleotide
Tamoxifen therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 13
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 30161160
- Full Text :
- https://doi.org/10.1371/journal.pone.0201606