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UGT1A polymorphisms associated with worse outcome in colorectal cancer patients treated with irinotecan-based chemotherapy

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Abstract

Purpose

To investigate the association between UDP-glucuronosyltransferase (UGT)1A polymorphisms and irinotecan-treatment efficacy in a Chinese population with metastatic colorectal cancer (mCRC).

Methods

The present study was based on a prospective multicenter trial of Chinese mCRC patients treated with irinotecan-based chemotherapy (NCT01282658, registered at http://www.clinicaltrials.gov). Fifteen single-nucleotide polymorphisms (SNPs) in four UGT1A genes were selected for genotyping in 164 patients. Kaplan–Meier and Cox regression analyses were used to assess the association between potential signatures and survival outcome.

Results

We found that UGT1A1*28 variant genotype was significantly associated with decreased progression-free survival (PFS) [adjusted hazard ratio (HR), 1.803; 95% confidence interval (CI), 1.217–2.671] and overall survival (OS) (adjusted HR 1.979; 95% CI 1.267–3.091) compared with wild-type genotype. Patients carrying (TA)7 allele showed a median PFS of 7.5 (95% CI 5.5–9.6) months compared with 9.8 (95% CI 8.6–10.9) months for patients with wild-type genotype. Median OSs were 13.3 (95% CI 10.3–16.2), and 20.8 (95% CI 18.7–23.0) months for (TA)6/7 or (TA)7/7, and (TA)6/6 patients, respectively. Similarly but more significantly, the copy number of haplotype III (composed by rs3755321-T, rs3821242-C, rs4124874-G and rs3755319-C) constructed among the selected SNPs also correlated with survival outcome.

Conclusions

UGT1A polymorphisms are predictive of survival outcome of irinotecan-treated Chinese mCRC patients. After validation, UGT1A polymorphisms might be helpful in facilitating stratification of mCRC patients for individualized treatment options.

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Funding

This study was funded by Grant no. 81372664 from the National Natural Science Foundation of China.

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Authors and Affiliations

  1. Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, Hubei, People’s Republic of China

    Qianqian Yu, Hong Qiu, Bo Liu, Liu Huang, Ping Peng & Xianglin Yuan

  2. Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, Hubei, People’s Republic of China

    Tao Zhang

  3. Department of Radiation and Medical Oncology, Zhongnan Hospital, Wuhan University, Wuhan, 430077, Hubei, People’s Republic of China

    Conghua Xie

  4. Department of Oncology, PuAi Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430034, Hubei, People’s Republic of China

    Jueping Feng

  5. Department of Surgery, Wuhan 8th Hospital, Wuhan, 430010, Hubei, People’s Republic of China

    Jigui Chen

  6. Hubei Cancer Hospital, Wuhan, 430079, Hubei, People’s Republic of China

    Aihua Zang

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  1. Qianqian Yu
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  2. Tao Zhang
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  3. Conghua Xie
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  4. Hong Qiu
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  8. Jueping Feng
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  9. Jigui Chen
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  10. Aihua Zang
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  11. Xianglin Yuan
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Correspondence to Xianglin Yuan.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The research was prospectively reviewed and approved by the Ethical Committee of Huazhong University of Science and Technology under reference number NCT01282658 (registered at http://www.clinicaltrials.gov).

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Yu, Q., Zhang, T., Xie, C. et al. UGT1A polymorphisms associated with worse outcome in colorectal cancer patients treated with irinotecan-based chemotherapy. Cancer Chemother Pharmacol 82, 87–98 (2018). https://doi.org/10.1007/s00280-018-3595-7

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