Correlation of MDR1 and ABCG2 genetic polymorphisms with the efficacy and adverse events of irinotecan chemotherapy in patients with colorectal cancer.
- Author:
Zhi-wei SUN
1
;
Xi-cheng WANG
;
Jing GAO
;
Jie LI
;
Yan-yan LI
;
Yun-zhi DANG
;
Lin SHEN
Author Information
- Publication Type:Journal Article
- MeSH: ATP Binding Cassette Transporter, Sub-Family B; ATP Binding Cassette Transporter, Sub-Family G, Member 2; ATP-Binding Cassette Transporters; genetics; ATP-Binding Cassette, Sub-Family B, Member 1; genetics; Adult; Aged; Camptothecin; analogs & derivatives; therapeutic use; Colorectal Neoplasms; drug therapy; genetics; Female; Humans; Male; Middle Aged; Neoplasm Proteins; genetics; Polymorphism, Single Nucleotide; Retrospective Studies; Treatment Outcome; Young Adult
- From: Chinese Journal of Gastrointestinal Surgery 2013;16(6):524-528
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the correlation of MDR1 and ABCG2 genetic polymorphisms with the efficacy and adverse events of irinotecan chemotherapy in patients with colorectal cancer (CRC).
METHODSClinical data of CRC patients treated with irinotecan-based chemotherapy in the Peking University Cancer Hospital between January 1996 and December 2011 were collected, and their blood samples were collected accordingly. Genomic DNA was extracted from blood samples. The following SNP detection of MDR1 and ABCG2 genes was conducted by direct sequencing method. The correlation of genetic SNPs with efficacy and toxicity of irinotecan treatment was further analyzed.
RESULTSAllele frequencies of MDR1 2677 G>T/A, ABCG2 421 C>A, 34 G>A, 376 C>T were comparable with previous studies. Genetic SNPs results from peripheral blood samples and tumor tissues were highly consistent. Patients carrying MDR1 2677 wild type had higher clinical benefit than those carrying mutant genotype, while the differences were not significant. The progression-free survival (PFS) was longer in wild-type patients as compared to mutant-type patients in second-line chemotherapy (P=0.012). There were no significant correlations between ABCG2 421 C>A, 34 G>A, 376 C>T and chemotherapy efficacy. No significant correlations were observed between MDR1 2677 G>T/A, ABCG2 421 C>A, ABCG2 34 G>A, ABCG2 376 C>T and irinotecan-related grade 3 and 4 neutropenia or diarrhea.
CONCLUSIONMDR1 2677 G>T/A may be served as a biomarker in predicting the efficacy of irinotecan chemotherapy in patients with colorectal cancer.