The influence of genetic variation of cytidine deaminase on hand-foot syndrome among colorectal cancer patients treated with capecitabine-based adjuvant chemother-apy regimens / 中国肿瘤临床

ABSTRACT

Objective:To investigate the association between grade 3 hand-foot syndrome(HFS)in colorectal cancer(CRC)patients treated with capecitabine and variation of cytidine deaminase(CDA)genes.Methods:The polymorphisms of the key gene CDA in-volved in capecitabine metabolism were genotyped and 149 CRC patients were included in this study.The association between these polymorphisms and susceptibility to HFS were analyzed.Additionally,peripheral blood mononuclear cells(PBMCs)of 91 CRC patients were collected for mRNA expression analysis, and the levels of mRNA expression according to different CDA genotypes were com-pared.Results:The prevalence of the polymorphism-451G>A,which is located in the promoter region of CDA,were correlated with HFS. The results were as follows GG genotype, 109 cases (73.15%); GA genotype, 38 cases (25.50%); and AA genotype, 2 cases (1.36%).The minor allele frequency of-451G>A was 0.14.The distribution of the three genotypes were in accordance with Hardy-Weinberg Equilibrium(P=0.516).Logistic analysis indicated that GA/AA genotypes were associated with grade 3 HFS(odds ratio=2.53, P=0.011).Additionally,another insert polymorphism-33delC located in the promoter region of CDA was in linkage disequilibrium with-451G>A (D'=0.92). Of the 91 PBMC mRNA expression analyses, the GA/AA genotype of-451G>A was associated with higher CDA mRNA expression compared with GG genotypes(4.01±0.53 vs.3.13±0.61,P<0.001).Conclusions:The polymorphism-451G>A of CDA may influence occurance of grade 3 HFS induced by capecitabine by influencing CDA mRNA expression.