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04.05.2018 | Original Article

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

verfasst von: Qianqian Yu, Tao Zhang, Conghua Xie, Hong Qiu, Bo Liu, Liu Huang, Ping Peng, Jueping Feng, Jigui Chen, Aihua Zang, Xianglin Yuan

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 1/2018

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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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Titel: UGT1A polymorphisms associated with worse outcome in colorectal cancer patients treated with irinotecan-based chemotherapy
verfasst von: Qianqian Yu
Tao Zhang
Conghua Xie
Hong Qiu
Bo Liu
Liu Huang
Ping Peng
Jueping Feng
Jigui Chen
Aihua Zang
Xianglin Yuan
Publikationsdatum: 04.05.2018
Verlag: Springer Berlin Heidelberg
Erschienen in: Cancer Chemotherapy and Pharmacology / Ausgabe 1/2018
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-018-3595-7

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18.04.2024 | Wirbelsäulenmetastase | Nachrichten

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

Abstract

Purpose

Methods

Results

Conclusions

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Update Onkologie

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusions

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