Relationship between UGT1A1 gene polymorphisms and irinotecan-induced severe adverse events
10.3760/cma.j.issn.0253-3766.2018.08.006
- VernacularTitle: 恶性肿瘤患者UGT1A1基因多态性与伊立替康所致严重不良反应的关系
- Author:
Xiaofei WANG
1
;
Chao MA
2
;
Fenfen GONG
1
;
Shanyong YI
3
;
Guochen XING
3
;
Kaijuan WANG
4
;
Qian YANG
4
;
Wei CAO
1
Author Information
1. Translational Medical Center, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou 450007, China
2. Department of Hepatobiliary and Pancreatic Surgery, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou 450007, China
3. Department of Oncology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou 450007, China
4. Henan Academy of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450052, China
- Publication Type:Clinical Trail
- Keywords:
Irinotecan;
UGT1A1;
Genetic polymorphisms;
Adverse drug reactions;
Delayed diarrhea;
Neutropenia
- From:
Chinese Journal of Oncology
2018;40(8):594-599
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the relationship between UGT1A1*6, UGT1A1*28, UGT1A1*60 and UGT1A1*93 polymorphisms and irinotecan-induced severe adverse reactions(grade 3-4 delayed diarrhea and neutropenia) in Chinese cancer patients.
Methods:A total of 141 cancer patients treated with irinotecan were enrolled in this study. Peripheral venous blood was collected and genomic DNA was extracted. The genetic polymorphisms of UGT1A1*6, UGT1A1*28, UGT1A1*60 and UGT1A1*93 were analyzed by PCR and direct sequencing. The adverse reactions during chemotherapy were observed and recorded. The incidence of severe adverse reactions was compared among patients with different genotypes.
Results:Among 141 patients, the cases with UGT1A1*6 GG, GA and AA genotypes were 71, 54 and 16, while those with UGT1A1*28 TA6/6, TA6/7 and TA7/7 genotypes were 105, 33 and 3, respectively. The cases with UGT1A1*60 AA, AC and CC genotypes were 52, 80 and 9, while those with UGT1A1*93 GG, GA and AA genotypes were 105, 32 and 4, respectively. The patients with grade 3-4 delayed diarrhea and neutropenia were 23 and 56, respectively. Multivariate logistic regression analysis showed that UGT1A1*6 and UGT1A1*60 genetic polymorphisms were independent factors influencing the occurrence of grade 3-4 delayed diarrhea. The risk of grade 3-4 delayed diarrhea in homozygous AA carriers of UGT1A1*6 increased 3.79 times compared with that in wild-type GG carriers (95%CI: 1.35-10.67). Moreover, the risk of grade 3-4 delayed diarrhea in homozygous CC carriers of UGT1A1*60 was 20.42 times compared with that in wild-type AA carriers (95%CI: 3.52-118.33). In addition, UGT1A1*28 genetic polymorphism was an independent factor of the occurrence of grade 3-4 neutropenia. The patients with homozygous TA7/7 carriers of UGT1A1*28 had an 1.61 times higher risk of grade 3-4 neutropenia compared with those with wild-type TA6/6 carriers (95%CI: 1.44-12.65). There was no correlation between UGT1A1*93 genetic polymorphism and severe adverse reactions caused by irinotecan.
Conclusion:The cancer patients who carried UGT1A1*6, UGT1A1*28 and UGT1A1*60 gene polymorphisms have high risk of severe adverse events caused by irinotecan-based chemotherapy.
