UGT1A1 Gene Polymorphisms and the Toxicities of FOLFIRI in Chinese Han Patients with Gastrointestinal Cancer

ISSN: 1875-5992 (Online)
ISSN: 1871-5206 (Print)

Volume 17, 14 Issues, 2017

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Anti-Cancer Agents in Medicinal Chemistry

Formerly: Current Medicinal Chemistry - Anti-Cancer Agents

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Michelle Prudhomme
Institut de Chimie de Clermont-Ferrand
Université Clermont Auvergne

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UGT1A1 Gene Polymorphisms and the Toxicities of FOLFIRI in Chinese Han Patients with Gastrointestinal Cancer

Anti-Cancer Agents in Medicinal Chemistry, 13(2): 235-241.

Author(s): Chen-fei Zhou, Tao Ma, Yang Su, Zheng-bao Ye, Jun Ji, Ying-yan Yu, Jun Zhang, Bing-ya Liu and Zheng-gang Zhu.

Affiliation: Department of Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No 197 Rui Jin Er Road, Shanghai 200025, People's Republic of China.


Background: Neutropenia and diarrhea are the common dose-limiting toxicities of irinotecan, and uridine diphosphate glucuronosyltransferases (UGTs) gene polymorphisms are considered to be one of the predictive markers of irinotecan related toxicities. This study aims to investigate the association between UGT1A1 gene polymorphisms and irinotecan related toxicities in Chinese Han gastrointestinal cancer patients receiving FOLFIRI regimen chemotherapy.

Methods: A total of 94 gastrointestinal cancer patients with metastasis (72 colon and rectum, 20 stomach, 1 pancreas and 1 duodenum), were enrolled from 2007 to 2010 in Shanghai Ruijin Hospital. All patients received standard dosage of FOLFIRI regimen (irinotecan 180mg/m2 d1, CF 200mg/m2 d1-d2, 5-FU 400mg/m2 d1-d2, followed by continuous infusion of 5-FU 600mg/m2 for 22h d1-d2, every 2 weeks). UGT1A1 gene polymorphisms (*60 -3279T > G, *93 -3156G > A, *28 -53TA6 > TA7, *6 211G > A) were detected by direct sequencing of DNA extracted from peripheral blood. The incidence of neutropenia, diarrhea, and time to severe toxicity were recorded. The relationship between UGT1A1 gene polymorphisms and toxicities was analyzed.

Results: The frequencies of UGT1A1*60 (-3279 G/G), UGT1A1*93 (-3156 A/A), UGT1A1*28 (-53 7/7) and UGT1A1*6 (211 A/A) homozygote were 6.4% (6/94), 1.1% (1/94), 1.1% (1/94) and 2.1% (2/94), respectively. The incidences of grade 3/4 neutropenia and diarrhea were 53.2% (50/94) and 12.8% (12/94), respectively. Comparing those with wild type, patients with UGT1A1*28 or *93 allele had significantly high risk of grade 3/4 diarrhea (6/7, 7/7 vs. 6/6: 27.8% vs. 9.2%, OR=3.791, P=0.034; G/A, A/A vs. G/G: 29.4% vs. 9.1%, OR=4.167, P=0.023). No relationship was found between UGT1A1 allele polymorphism and grade 3/4 neutropenia. The baseline serum total bilirubin was elevated in UGT1A1*28, *93 allele carriers and *60 homozygote, but with no relationship with severe toxicities.

Conclusion: In Chinese Han gastrointestinal cancer patients receiving standard FOLFIRI regimen, UGT1A1*28 or *93 allele carriers may have high risk of severe diarrhea.


UGT1A1 polymorphism, Irinotecan, Predictive marker, Molecular diagnosis, Gastrointestinal cancer.

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Article Details

Volume: 13
Issue Number: 2
First Page: 235
Last Page: 241
Page Count: 7
DOI: 10.2174/1871520611313020008
Price: $58

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