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 involved 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 compared.

  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 HardyWeinberg 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.