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Genetic polymorphisms as predictive biomarkers of adverse events during preoperative chemotherapy in esophageal cancer

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Abstract

Purpose

This study aimed to explore associations between genetic polymorphisms and adverse effects due to preoperative chemotherapy with docetaxel, cisplatin, and fluorouracil (DCF) for esophageal cancer.

Methods

Preoperative DCF (docetaxel, 70 mg/m2/day, day 1; cisplatin, 70 mg/m2/day, day 1; fluorouracil, 750 mg/m2/day, days 1–5) was repeated every 3 weeks for up to three cycles. Genoty** of nine candidate genetic polymorphisms was conducted using blood samples from the enrolled patients.

Results

According to a multivariable analysis evaluating 50 patients, grade 3 or worse neutropenia was more likely to occur in those with the ABCC2-24C/T or T/T genotype (rs717620) (OR, 5.30, P = 0.013). Additionally, patients with the TYMS 3′-UTR 0 bp/0 bp genotype (rs151264360) showed a trend toward grade 3 or worse hyponatremia (OR, 0.16, P = 0.005). Grade 2 or worse thrombocytopenia was more likely to occur in patients with the TNF-α-1031C/T or T/T genotype (rs1799964) (OR, 6.30, P = 0.016) and IL-6-634C/C genotype (rs1800796) (OR, 0.18, P = 0.034), and grade 2 or worse anemia was more likely to occur in patients with the MCP-1-2518G/G genotype (rs1024611) (OR, 0.19, P = 0.027).

Conclusions

ABCC2-24C > T (rs717620), TYMS 3′-UTR 6-bp indel (rs151264360), TNF-α-1031T > C (rs1799964) as well as IL-6-634G > C (rs1800796), and MCP-1-2518A > G (rs1024611) polymorphisms might serve as independent and predictive biomarkers for neutropenia, hyponatremia, thrombocytopenia, and anemia, respectively, during preoperative chemotherapy with docetaxel, cisplatin, and fluorouracil for patients with esophageal cancer.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Authors and Affiliations

  1. Department of Clinical Oncology and Chemotherapy, Nagoya University Hospital, Nagoya, Japan

    Yao Liang, Osamu Maeda & Yuichi Ando

  2. Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan

    Kazushi Miyata & Shizuki Sugita

  3. Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan

    Mitsuro Kanda, Dai Shimizu & Yasuhiro Kodera

  4. Department of Advanced Medicine, Nagoya University Hospital, Nagoya, Japan

    Kazuki Nishida

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  1. Yao Liang
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Correspondence to Osamu Maeda.

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Conflict of interest

Yasuhiro Kodera reports personal fees from Ono Pharmaceutical Co., Ltd. and Daiichi Sankyo Co., Ltd. and research funds from Chugai Pharmaceutical Co., Ltd., Tiho Pharmaceutical Co., Ltd., and Yakult Honsha Co., Ltd. Yuichi Ando reports grants and personal fees from Chugai Pharmaceutical Co., Ltd., personal fees from Bayer Holding Ltd., research funds from Beigene, and grants from Geo Holdings outside the submitted work. The other authors have no conflicts of interest to declare.

Ethical approval

This study was conducted in accordance with the Ethical Guidelines for Medical and Biological Research Involving Human Subjects (Ministry of Health, Labor and Welfare, Japan) and the Declaration of Helsinki. This study was approved by the Institutional Review Board (approval no. 2021-0091). All patients provided written informed consent.

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Liang, Y., Maeda, O., Miyata, K. et al. Genetic polymorphisms as predictive biomarkers of adverse events during preoperative chemotherapy in esophageal cancer. Cancer Chemother Pharmacol 93, 121–127 (2024). https://doi.org/10.1007/s00280-023-04607-7

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