Effect of CYP1A1 polymorphism on the clinical efficacy of docetaxel combined with capecitabine in the treatment of metastatic breast cancer

Abstract

Objective In recurrent metastatic breast cancer (MBC) patients treated with docetaxel combined with capecitabine, we aimed to investigate the correlation between single nucleotide polymorphisms (SNPs) of cytochrome 450 (CYP450) gene and individual differences in clinical outcomes. Methods Sixty-nine MBC patients who were treated with docetaxel plus capecitabine were included in this study. And 79 SNPs in CYP450 gene, whose minorallele frequency (MAF) was >10% in the Chinese population were genotyped by TOF mass spectrometry and direct sequencing. The associations between these 79 SNPs and clinical outcomes were further analyzed. Results Only the CYP1A1 rs1048943 (Ile462Val) among 79 SNPs was signiflcantly associated with progression-free survival (PFS, P=0.000). There was no significant correlation between other SNPs and treatment response rate and overall survival (OS). The rs1048943 (Ile462Val) site was included in the COX risk ratio model for further analysis. After adjustment, we conflrmed that it was an independent predictor of PFS (P=0.004). Conclusion CYP1A1 rs1048943 polymorphism is probably an independent prognostic marker for survival outcome in MBC patients treated with docetaxel plus capecitabine chemotherapy. Key words: Breast cancer; Cytochrome P450; Polymorphism