Molecular Pharmacology Section, National Cancer Institute, Bethesda, MD, USA.
Ther Clin Risk Manag. 2010 Nov 19;6:579-83. doi: 10.2147/TCRM.S14303.
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.
先前在一项全基因组关联研究中发现,CYP2C8(rs1934951)的单核苷酸多态性(SNP)是接受双膦酸盐(BPs)治疗多发性骨髓瘤患者发生颌骨骨坏死(ONJ)的风险因素。为了确定相同的 SNP 是否也与接受 BP 治疗前列腺癌骨转移的男性发生 ONJ 有关,我们对 100 名接受 BP 治疗骨转移的去势抵抗性前列腺癌男性进行了基因分型,其中 17 名发生了 ONJ。发生 ONJ 和未发生 ONJ 的患者具有重要的临床特征,包括双膦酸盐治疗的类型和持续时间。我们发现变异等位基因与 ONJ 的发生之间没有显著相关性(OR = 0.63,95%CI:0.165-2.42,P > 0.47)。CYP2C8(rs1934951)中的这种内含子 SNP 似乎不是前列腺癌男性发生与 BP 相关的 ONJ 的危险因素。需要注意的是,这只是第二项研究探讨与 BP 相关的 ONJ 相关的遗传学,也是第一项在前列腺癌男性中进行的研究。需要更多的研究来确定可能预测这种重要临床状况发生的遗传风险因素。