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

• Published in: Cancer chemotherapy and pharmacology Vol. 69; no. 6; pp. 1617 - 1624
• Main Authors: Uchiyama, Toshitaka, Kanno, Hitoshi, Ishitani, Ken, Fujii, Hisaichi, Ohta, Hiroaki, Matsui, Hideo, Kamatani, Naoyuki, Saito, Kayoko
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.06.2012; Springer; Springer Nature B.V
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic agents; Antineoplastic Agents - adverse effects; Area Under Curve; Biological and medical sciences; biomarkers; Cancer Research; Chemotherapy; Endometrium; Female; Genital Neoplasms, Female - drug therapy; Genotype; Genotyping; Hematologic and hematopoietic diseases; Humans; Leukocytes (neutrophilic); Medical sciences; Medicine; Medicine & Public Health; Middle Aged; Neutropenia; Neutropenia - chemically induced; Oncology; Original Article; Other diseases. Hematologic involvement in other diseases; Ovarian cancer; Pharmacology. Drug treatments; Pharmacology/Toxicology; Polymorphism, Single Nucleotide; Single-nucleotide polymorphism; Steroid Hydroxylases - genetics; Taxoids - adverse effects; Taxoids - blood; Uterine cancer; Uterus; DMET; Gynecological cancers; Docetaxel; Neutropenia; Antineoplastic agent; Leukopenia; Taxane derivatives; Hemopathy; Antimitotic; Cancer; Female genital diseases
• ISSN: 0344-5704; 1432-0843
• DOI: 10.1007/s00280-012-1872-4

Purpose 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. Methods As a first step, AUC of docetaxel was examined in 10 patients and 1,936 SNPs of 225 genes were genotyped using DMET Plus™ genotyping systems. Results 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. Conclusions This SNP in CYP39A1 may be a useful biomarker for predicting the risk of docetaxel-induced neutropenia.