Qianqian Yu1, Tao Zhang2, Conghua Xie3, Hong Qiu1, Bo Liu1, Liu Huang1, Ping Peng1, Jueping Feng4, Jigui Chen5, Aihua Zang6, Xianglin Yuan7. 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. 2. Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, Hubei, People's Republic of China. 3. Department of Radiation and Medical Oncology, Zhongnan Hospital, Wuhan University, Wuhan, 430077, Hubei, People's Republic of China. 4. Department of Oncology, PuAi Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430034, Hubei, People's Republic of China. 5. Department of Surgery, Wuhan 8th Hospital, Wuhan, 430010, Hubei, People's Republic of China. 6. Hubei Cancer Hospital, Wuhan, 430079, Hubei, People's Republic of China. 7. 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. xlyuan1020@163.com.
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.
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.
Authors: Zheng Liu; Jennifer H Martin; Winston Liauw; Sue-Anne McLachlan; Emma Link; Anetta Matera; Michael Thompson; Michael Jefford; Rod J Hicks; Carleen Cullinane; Athena Hatzimihalis; Ian Campbell; Simone Crowley; Phillip J Beale; Christos S Karapetis; Timothy Price; Mathew E Burge; Michael Michael Journal: Eur J Clin Pharmacol Date: 2021-09-04 Impact factor: 2.953
Authors: Ryan S Nelson; Nathan D Seligson; Sal Bottiglieri; Estrella Carballido; Alex Del Cueto; Iman Imanirad; Richard Levine; Alexander S Parker; Sandra M Swain; Emma M Tillman; J Kevin Hicks Journal: Cancers (Basel) Date: 2021-03-29 Impact factor: 6.639