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Prognostic impact of a single-nucleotide polymorphism near the CTSO gene in hormone receptor-positive breast cancer patients

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Abstract

Background

Tamoxifen can reduce the occurrence of breast cancer by a half in high-risk women. Recently, a genome-wide association study identified two single-nucleotide polymorphisms (SNPs) near or in the CTSO and ZNF423 genes that were associated with breast cancer risk during tamoxifen therapy. We hypothesized that these two SNPs could be associated with increased recurrence in breast cancer patients who received adjuvant tamoxifen therapy.

Methods

A total of 586 breast carcinomas were available for SNP genotyping assays. TaqMan pre-designed SNP genotyping assays were used to identify the presence of CTSO rs10030044 and ZNF423 rs8060157. We then investigated the relationship between CTSO rs10030044 genotypes and mRNA expression levels of CTSO and BRCA1 in 290 breast cancer patients.

Results

We found a positive correlation between the variant GG genotype of CTSO rs10030044 and shorter disease-free survival, or overall survival in hormone receptor-positive breast cancer patients receiving adjuvant tamoxifen therapy. In contrast, this genotype was not associated with prognosis in hormone receptor-negative breast cancer patients. Multivariate Cox regression analysis revealed that this genotype was an independent factor indicating a poor prognosis in hormone receptor-positive breast cancer patients receiving adjuvant tamoxifen therapy. No association was found between CTSO genotype and mRNA expression of CTSO and BRCA1. ZNF423 rs8060157 genotype was not associated with prognosis in this study.

Conclusion

We show that a SNP near the CTSO gene is a poor prognostic factor in breast cancer although further research might help to reveal the factors linking this genotype and prognosis.

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Acknowledgments

This work was, in part, supported by JSPS KAKENHI Grant Number 15K10061.

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Authors and Affiliations

  1. Department of Oncology, Immunology and Surgery, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan

    Yukari Hato, Naoto Kondo, Nobuyasu Yoshimoto, Yumi Endo, Tomoko Asano, Yu Dong, Mayumi Nishimoto, Yoshitaka Fujii, Ryoichi Nakanishi & Tatsuya Toyama

  2. Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan

    Satoru Takahashi

Authors
  1. Yukari Hato
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  2. Naoto Kondo
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  3. Nobuyasu Yoshimoto
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  4. Yumi Endo
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  5. Tomoko Asano
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  6. Yu Dong
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  7. Mayumi Nishimoto
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  8. Satoru Takahashi
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  9. Yoshitaka Fujii
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  10. Ryoichi Nakanishi
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  11. Tatsuya Toyama
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Corresponding author

Correspondence to Tatsuya Toyama.

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Conflict of interest

Yukari Hato, Naoto Kondo, Nobuyasu Yoshimoto, Yumi Endo, Tomoko Asano, Yu Dong, Mayumi Nishimoto, Satoru Takahashi, Yoshitaka Fujii, Ryoichi Nakanishi have no conflict of interest. Tatsuya Toyama received a research grant from Takeda Pharmaceutical Co., Ltd., Daiichi Sankyo Healthcare Co., Ltd. and Novartis Pharma K.K.

Electronic supplementary material

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10147_2015_913_MOESM1_ESM.pptx

Supplementary material 1 (PPTX 59 kb). Supplemental Fig. 2 Kaplan–Meier survival curves of breast cancer patients categorized by the three genotypes (TT, GT, and GG) of CTSO rs10030044. Graphs show disease-free survival (DFS) (G) and overall survival (OS) (H) for hormone receptor-positive breast cancer patients receiving adjuvant tamoxifen therapy

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Hato, Y., Kondo, N., Yoshimoto, N. et al. Prognostic impact of a single-nucleotide polymorphism near the CTSO gene in hormone receptor-positive breast cancer patients. Int J Clin Oncol 21, 539–547 (2016). https://doi.org/10.1007/s10147-015-0913-5

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  • DOI: https://doi.org/10.1007/s10147-015-0913-5

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