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Association between ABCC2 polymorphism and hematological toxicity in patients with esophageal cancer receiving platinum plus 5-fluorouracil therapy

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Abstract

Background

Platinum agents are taken up into cells by copper transporter (CTR) 1 (gene code: SLC31A1) and are excreted from cells by copper-transporting P-type adenosine triphosphatase (ATP7B) and multidrug resistance-associated protein (MRP) 2 (gene code: ABCC2). In addition, glutathione S transferase (GST) P1 is involved in the metabolism of platinum agents. The present study aimed to determine whether the rate of grade 3–4 hematological toxicity associated with platinum plus 5-fluorouracil (5-FU) therapy in 239 patients with esophageal cancer was affected by the SLC31A1 rs10981694A>C and rs12686377G>T, ATP7B rs9535828A>G, GSTP1 rs1695A>G, and ABCC2 −24C>T polymorphisms.

Methods

Chemotherapy consisted of protracted infusion of 5-FU (800 mg/m2/day) on days 1–5 and cisplatin or nedaplatin (80 mg/m2/day) on day 1.

Results

A total of 82 of 239 patients developed grade 3–4 hematological toxicity after chemotherapy. Univariate analysis showed that ABCC2 −24C/T + T/T genotypes (P = 0.038), radiation therapy (P = 0.013), baseline white blood cell count < 6000/μL (P = 0.003), and baseline neutrophil count < 3900/μL (P = 0.021) were statistically significant predictors of grade 3–4 hematological toxicity. Multivariate analysis revealed that ABCC2 −24C/T + T/T genotypes (P = 0.036), radiation therapy (P = 0.005), and baseline white blood cell count < 6000/μL (P < 0.001) were significant risk factors.

Conclusions

We determined that ABCC2 −24C>T is significantly associated with grade 3–4 hematological toxicity after platinum plus 5-FU therapy. These findings might contribute to improved treatment strategies for patients with esophageal cancer.

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Acknowledgements

This work was supported by a grant (No. 20H01096) from the Japan Society for the Promotion of Science, Tokyo, Japan.

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Authors and Affiliations

  1. Department of Pharmacy, Akita University Hospital, 1-1-1 Hondo, Akita, 010-8543, Japan

    Kazuma Fujita & Masatomo Miura

  2. Department of Esophageal Surgery, Akita University Hospital, Akita, Japan

    Satoru Motoyama, Yusuke Sato, Akiyuki Wakita, Yushi Nagaki & Yoshihiro Minamiya

  3. Department of Comprehensive Cancer Control, Akita University Graduate School of Medicine, Akita, Japan

    Satoru Motoyama

Authors
  1. Kazuma Fujita
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  2. Satoru Motoyama
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  3. Yusuke Sato
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  4. Akiyuki Wakita
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  5. Yushi Nagaki
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  6. Yoshihiro Minamiya
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  7. Masatomo Miura
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Contributions

KF, SM, YS, AW, YN, YM, and MM participated in the design of the study and reviewed the results. SM, YS, AW, YN, and YM were responsible for patient accrual and were involved in data acquisition. KF performed the genotyping. KF, SM, and MM were responsible for the statistical analyses. YS, AW, YN, and YM drafted the manuscript. AS, KS, TN, and KI helped draft the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Masatomo Miura.

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Ethical Statement

The study was performed in accordance with the ethical standards of the Declaration of Helsinki and its subsequent amendments.

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No author has any conflict of interest to declare.

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Signed informed consent was obtained from all patients.

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Fujita, K., Motoyama, S., Sato, Y. et al. Association between ABCC2 polymorphism and hematological toxicity in patients with esophageal cancer receiving platinum plus 5-fluorouracil therapy. Esophagus 19, 146–152 (2022). https://doi.org/10.1007/s10388-021-00865-7

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  • DOI: https://doi.org/10.1007/s10388-021-00865-7

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