An SNP in CYP39A1 is associated with severe neutropenia induced by docetaxel

Docetaxel is one of the most widely used chemotherapy drugs for gynecological cancers. A dose-limiting factor of docetaxel is severe neutropenia, and previous reports showed that grade 4 neutropenia was observed in approximately 70 % of Japanese patients treated with docetaxel. In order to elucidate a valid biomarker for docetaxel-induced neutropenia, we analyzed 42 Japanese patients with gynecological cancers such as ovarian cancer and endometrial cancer of the uterus. As a first step, AUC of docetaxel was examined in 10 patients and 1,936 SNPs of 225 genes were genotyped using DMET Plus (TM) genotyping systems. The first screening revealed that 28 SNPs were associated with the AUC (P < 0.05), and we analyzed the associations between the 28 SNPs and neutrophil counts in the other 32 patients, with the result that CYP39A1 (rs7761731) was found to be the only SNP significantly associated (P = 0.049 OR = 9.0) with the incidence of grade 4 neutropenia among 28 SNPs. This SNP in CYP39A1 may be a useful biomarker for predicting the risk of docetaxel-induced neutropenia.