A SNP in CYP2C8 is not associated with the development of bisphosphonate-related osteonecrosis of the jaw in men with castrate-resistant prostate cancer
Bevin C English1, Caitlin E Baum1, David E Adelberg3, Tristan M Sissung2, Paul G Kluetz3, William L Dahut3, Douglas K Price1, William D Figg1,2
1Molecular Pharmacology Section, 2Clinical Pharmacology Research Core, 3Medical Oncology Branch, National Cancer Institute, Bethesda, MD, USA
Abstract: A single nucleotide polymorphism (SNP) in CYP2C8 (rs1934951), was previously identified in a genome-wide association study as a risk factor for the development of osteonecrosis of the jaw (ONJ) in patients receiving bisphosphonates (BPs) for multiple myeloma. To determine if the same SNP is also associated with the development of ONJ in men receiving BPs for bone metastases from prostate cancer, we genotyped 100 men with castrate-resistant prostate cancer treated with bisphosphonates for bone metastases, 17 of whom developed ONJ. Important clinical characteristics, including type and duration of bisphosphonate therapy, were consistent among those who developed ONJ and those who did not. We found no significant correlation between the variant allele and the development of ONJ (OR = 0.63, 95% CI: 0.165–2.42, P > 0.47). This intronic SNP in CYP2C8 (rs1934951) does not seem to be a risk factor for the development of bisphosphonate-related ONJ in men with prostate cancer. It is important to note that this is only the second study to investigate the genetics associated with BP-related ONJ and the first to do so in men with prostate cancer. More studies are needed to identify genetic risk factors that may predict the development of this important clinical condition.
Keywords: bisphosphonates, ONJ, CYP2C8, polymorphism
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