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Cancer Chemother Pharmacol. 2017 Jun;79(6):1109-1117. doi: 10.1007/s00280-017-3306-9. Epub 2017 May 13.

UGT1A1 polymorphisms with irinotecan-induced toxicities and treatment outcome in Asians with Lung Cancer: a meta-analysis.

Chen X1,2,3, Liu L2,3, Guo Z1,3, Liang W1,3, He J1,3, Huang L2,3, Deng Q2,3, Tang H2,3, Pan H2,3, Guo M1,2,3, Liu Y1,3, He Q1,3, He J4,5,6.

Author information

1
Department of Thoracic Surgery, Guangzhou Institute of Respiratory Disease and State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, No 151, Yanjiang Rd, Guangzhou, 510120, Guangdong, People's Republic of China.
2
The Translational Medicine Laboratory, State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People's Republic of China.
3
Key Cite of National Clinical Research Center for Respiratory Disease, Guangzhou, People's Republic of China.
4
Department of Thoracic Surgery, Guangzhou Institute of Respiratory Disease and State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, No 151, Yanjiang Rd, Guangzhou, 510120, Guangdong, People's Republic of China. drjianxing.he@gmail.com.
5
The Translational Medicine Laboratory, State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People's Republic of China. drjianxing.he@gmail.com.
6
Key Cite of National Clinical Research Center for Respiratory Disease, Guangzhou, People's Republic of China. drjianxing.he@gmail.com.

Abstract

Previous studies of irinotecan pharmacogenetics have shown that the UGT1A1*28 polymorphism has an effect on irinotecan (IRI)-induced toxicities in Caucasians. Yet compared with the UGT1A1*6 mutation, the UGT1A1*28 occurs at a much lower frequency in the Asians. Whether UGT1A1*6 and UGT1A1*28 are associated with IRI-induced neutropenia, diarrhea and IRI-based chemotherapy tumor response (TR) in Asians with lung cancer remains controversial. In this meta-analysis, we found a higher risk of neutropenia and diarrhea with IRI-based chemotherapy in Asians with lung cancer carrying the UGT1A1*6 polymorphism. However, UGT1A1*28 showed a weak correlation with diarrhea, but no significant correlation with neutropenia. Neither UGT1A1*6 nor UGT1A1*28 is associated with IRI-based chemotherapy TR. These data suggest that the UGT1A1*28 polymorphism may not be a suitable biomarker to predict IRI-induced toxicities and chemotherapy TR in Asians, while UGT1A*6 polymorphism is associated with a higher risk of IRI-induced neutropenia and diarrhea, but not IRI-based chemotherapy TR.

KEYWORDS:

Asians; Irinotecan; Lung cancer; Toxicity; Tumor response; UGT1A1 polymorphism

PMID:
28502040
DOI:
10.1007/s00280-017-3306-9
[Indexed for MEDLINE]

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