Oncotarget

Research Papers:

GSTP1 rs1695 is associated with both hematological toxicity and prognosis of ovarian cancer treated with paclitaxel plus carboplatin combination chemotherapy: a comprehensive analysis using targeted resequencing of 100 pharmacogenes

Tomoko Yoshihama, Koya Fukunaga, Akira Hirasawa, Hiroyuki Nomura, Tomoko Akahane, Fumio Kataoka, Wataru Yamagami, Daisuke Aoki and Taisei Mushiroda _

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Oncotarget. 2018; 9:29789-29800. https://doi.org/10.18632/oncotarget.25712

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Abstract

Tomoko Yoshihama1,2, Koya Fukunaga1, Akira Hirasawa2, Hiroyuki Nomura2, Tomoko Akahane2, Fumio Kataoka2, Wataru Yamagami2, Daisuke Aoki2 and Taisei Mushiroda1

1Laboratory for Pharmacogenomics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan

2Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo, Japan

Correspondence to:

Taisei Mushiroda, email: mushiroda@riken.jp

Keywords: pharmacogenomics; carboplatin; ovarian cancer; next-generation sequencer; targeted resequencing

Received: April 07, 2018    Accepted: June 13, 2018    Published: July 03, 2018

ABSTRACT

Purpose: To find genetic variants that predicted toxicity and/or efficacy of paclitaxel plus carboplatin combination therapy (TC therapy).

Patients and methods: In a retrospective case-control study, we analyzed 320 patients who had received TC therapy for gynecological cancers (ovarian, fallopian tube, peritoneal, uterine, and cervical cancers) and collected their germline DNA. We performed a comprehensive pharmacogenomic analysis using a targeted resequencing panel of 100 pharmacogenes. For 1,013 variants passing QC, case-control association studies and survival analyses were conducted.

Results: GSTP1 rs1695 showed the smallest p value for hematotoxicity association, and the 105Ile wild type allele had a significantly higher risk of severe hematotoxicity (neutropenia G4, thrombocytopenia ≥ G3 and anemia ≥ G3) than the 105Val allele (p=0.00034, odds ratio=5.71 (95% confidence interval:1.77-18.44)). Next, we assessed 5-year progression-free survival (PFS) and overall survival (OS) in 56 advanced ovarian cancer patients who received tri-weekly TC as a first-line chemotherapy. Patients with the 105Ile/105Ile genotype showed significantly better PFS (p=0.00070) and OS (p=0.0012) than those with the 105Ile/105Val or 105Val/105Val genotype.

Conclusion: Our study indicates that the GSTP1 rs1695 105Ile/105Ile genotype is associated with both severe hematotoxicity and high efficacy of TC therapy, identifying a possible prognostic indicator for patients with TC therapy.


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