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, Taisei Mushiroda

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

Original languageEnglish
Pages (from-to)29789-29800
Number of pages12
JournalOncotarget
Volume9
Issue number51
DOIs
Publication statusPublished - Jul 1 2018
Externally publishedYes

Fingerprint

Carboplatin
Paclitaxel
Combination Drug Therapy
Ovarian Neoplasms
Fallopian Tube Neoplasms
Genotype
Disease-Free Survival
Case-Control Studies
Alleles
Therapeutics
Survival
Survival Analysis
Neutropenia
Uterine Cervical Neoplasms
Thrombocytopenia
Anemia
Odds Ratio
Confidence Intervals
Drug Therapy
DNA

Keywords

  • Carboplatin
  • Next-generation sequencer
  • Ovarian cancer
  • Pharmacogenomics
  • Targeted resequencing

ASJC Scopus subject areas

  • Oncology

Cite this

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. / Yoshihama, Tomoko; Fukunaga, Koya; Hirasawa, Akira; Nomura, Hiroyuki; Akahane, Tomoko; Kataoka, Fumio; Yamagami, Wataru; Aoki, Daisuke; Mushiroda, Taisei.

In: Oncotarget, Vol. 9, No. 51, 01.07.2018, p. 29789-29800.

Research output: Contribution to journalArticle

Yoshihama, Tomoko ; Fukunaga, Koya ; Hirasawa, Akira ; Nomura, Hiroyuki ; Akahane, Tomoko ; Kataoka, Fumio ; Yamagami, Wataru ; Aoki, Daisuke ; Mushiroda, Taisei. / 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. In: Oncotarget. 2018 ; Vol. 9, No. 51. pp. 29789-29800.
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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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T1 - GSTP1 rs1695 is associated with both hematological toxicity and prognosis of ovarian cancer treated with paclitaxel plus carboplatin combination chemotherapy

T2 - A comprehensive analysis using targeted resequencing of 100 pharmacogenes

AU - Yoshihama, Tomoko

AU - Fukunaga, Koya

AU - Hirasawa, Akira

AU - Nomura, Hiroyuki

AU - Akahane, Tomoko

AU - Kataoka, Fumio

AU - Yamagami, Wataru

AU - Aoki, Daisuke

AU - Mushiroda, Taisei

PY - 2018/7/1

Y1 - 2018/7/1

N2 - 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.

AB - 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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KW - Pharmacogenomics

KW - Targeted resequencing

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