Oncotarget

Research Papers:

Polymorphisms of ESR1, UGT1A1, HCN1, MAP3K1 and CYP2B6 are associated with the prognosis of hormone receptor-positive early breast cancer

Sung-Hsin Kuo _, Shi-Yi Yang, San-Lin You, Huang-Chun Lien, Ching-Hung Lin, Po-Han Lin and Chiun-Sheng Huang

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Oncotarget. 2017; 8:20925-20938. https://doi.org/10.18632/oncotarget.14995

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Abstract

Sung-Hsin Kuo1,5,6,7, Shi-Yi Yang8, San-Lin You9,10, Huang-Chun Lien2, Ching-Hung Lin1,6, Po-Han Lin3, Chiun-Sheng Huang4

1Department of Oncology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan

2Department of Pathology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan

3Department of Medical Genetics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan

4Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan

5Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan

6Cancer Research Center, National Taiwan University College of Medicine, Taipei, Taiwan

7National Taiwan University Cancer Center, National Taiwan University College of Medicine, Taipei, Taiwan

8Graduate Institute of Epidemiology, College of Public Health, National Taiwan University, Taipei, Taiwan

9School of Medicine, College of Medicine, Fu-Jen Catholic University, New Taipei, Taiwan

10Big Data Research Center, Fu-Jen Catholic University, New Taipei, Taiwan

Correspondence to:

Chiun-Sheng Huang, email: [email protected]

Keywords: genetic polymorphism, GWAS, breast cancer, prognostic factor, survival

Received: August 01, 2016    Accepted: January 03, 2017    Published: February 02, 2017

ABSTRACT

In this study, we investigated whether single nucleotide polymorphisms (SNPs) identified by genome-wide association study (GWAS) (MAP3K1, FGFR2, TNRC9, HCN1, and 5p12), and SNPs involved in the metabolism of estrogen (CYP19, COMT, ESR1, and UGT1A1), tamoxifen (CYP2C9, CYP2C19, CYP3A5, and CYP2D6), and chemotherapeutic agents (ABCB1, ALDH3A1, and CYP2B6) are associated with the prognoses of 414 hormone receptor (HR)-positive early breast cancers with negative or 1 to 3 nodal metastases. At a median follow-up period of 10.6 years, 363 patients were alive, and 51 (12.3%) had died. Multiple-adjusted hazard ratios (aHRs) and the corresponding 95% confidence intervals for distant disease-free survival (DDFS), disease-free survival (DFS), and overall survival (OS) in association with the genotypes of 34 SNPs from the above-mentioned 16 genes were evaluated, using the stepwise selection Cox model. We found that the SNP, ESR1-codon325 rs1801132 (G/G+G/C), was associated with a longer DDFS, whereas UGT1A1 rs4148323 (A/A+A/G), and HCN1 rs981782 (A/A+A/C) were significantly associated with poorer DDFS. MAP3K1 rs889312 (C/C) and CYP2B6 rs3211371 (T/C) were significantly associated with poor DFS, DDFS and OS. Among premenopausal women, MAP3K1 rs889312 (C/C), CYP2B6 rs3211371 (T/C), CYP2B6 rs4802101 (T/T), ABCB1 rs2032582 (C/C), and ALDH3A1 rs2231142 (G/G) were significantly associated with poor DDFS, DFS, or OS. Our results provide additional evidence that genetic polymorphisms observed in SNPs are associated with the prognoses of patients with HR-positive breast cancers; this may indicate different treatment strategies for these patients.


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