Cytochrome 450 1B1 (CYP1B1) polymorphisms associated with response to docetaxel in Castration-Resistant Prostate Cancer (CRPC) patients
- Equal contributors
1 Department of Medical Oncology, Pisa University Hospital, Pisa, Italy
2 Grosseto Civic Hospital, Grosseto, Italy
3 Division of Pharmacology and Chemotherapy, Department of Internal Medicine, University of Pisa; Via Roma 55, 56100 Pisa, Italy
4 Department of Medical Oncology, VU University Medical Center, De Boelelaan 1117, 1081HV, Amsterdam, The Netherlands
5 Medical Oncology Branch, National Cancer Institute, 9000 Rockville Pike Building 10, Room 5A01, Bethesda, MD 20892, US
BMC Cancer 2010, 10:511 doi:10.1186/1471-2407-10-511Published: 27 September 2010
The selection of patients according to key genetic characteristics may help to tailor chemotherapy and optimize the treatment in Castration-Resistant Prostate Cancer (CRPC) patients. Functional polymorphisms within the cytochrome P450 1B1 (CYP1B1) gene have been associated with alterations in enzymatic expression and activity and may change sensitivity to the widely used docetaxel regimen.
CYP1B1 genotyping was performed on blood samples of 60 CRPC patients treated with docetaxel, using TaqMan probes-based assays. Association between CYP1B1-142C>G (leading to the 48ArgGly transition), 4326C>G (432LeuVal), and 4390A>G (453AsnSer) polymorphisms and treatment response, progression-free-survival (PFS) and overall-survival (OS) was estimated using Pearson χ2 test, Kaplan-Meier curves and Log-rank test.
Patients carrying the CYP1B1-432ValVal genotype experienced a significantly lower response-rate (P = 0.014), shorter progression-free-survival (P = 0.032) and overall-survival (P < 0.001). Multivariate analyses and correction for multiple comparisons confirmed its prognostic significance for OS. No significant associations were found among other polymorphisms and both response and clinical outcome.
CYP1B1-4326C>G (432LeuVal) polymorphism emerged as possible predictive marker of response and clinical outcome to docetaxel in CRPC patients and may represent a potential new tool for treatment optimization. Larger prospective trials are warranted to validate these findings, which might be applied to the future practice of CRPC treatment.