维生素D受体基因多态性与前列腺癌根治术后生化复发的相关性分析

Association of Vitamin D Receptor Gene Polymorphisms with Biochemical Recurrence of Prostatic Cancer after Radical Prostatectomy

目的探讨维生素D受体(VDR)基因外显子FokⅠ、TaqⅠ位点多态性与前列腺癌根治术后生化复发的相关性。方法以2008年1月-2013年1月于我院接受前列腺癌根治术的280例患者为研究对象,术后随访至死亡或至2018年1月,根据肿瘤是否生化复发,分为观察组(生化复发,n=78)和对照组(未生化复发,n=202)。于根治术前,采集两组外周血,应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)检测FokⅠ、TaqⅠ位点多态性,对比两组上述位点等位基因及基因型的频率分布。结果两组FokⅠ、TaqⅠ位点多态性均符合Hardy-Weinberg遗传平衡。两组FokⅠ位点基因型及等位基因分布均有明显差异(P<0.05),以携带FF基因型患者为参照,携带Ff、ff基因型患者生化复发风险明显增加(OR=2.966,95%CI=1.389～6.332;OR=4.590,95%CI=2.014～10.463),携带f等位基因的患者生化复发风险明显增加(OR=2.059,95%CI=1.412～3.001)。两组TaqⅠ位点基因型及等位基因分布均无明显差异(P>0.05)。多因素Cox分析显示,FokⅠ位点基因型为FF患者发生生化复发的独立保护因素(P<0.05)。结论 VDR基因外显子FokⅠ多态性可能与前列腺癌根治术后生化复发有一定相关性,携带f等位基因可能是生化复发的危险因素,基因型FF可能是生化复发的保护因素。

Objective To investigate the correlations between single nucleotide polymorphisms（ SNPs） in FokⅠ and TaqⅠ in vitamin D receptor（ VDR） genes and biochemical recurrence of prostatic cancer after radical prostatectomy.Methods Two hundred and eighty patients diagnosed with prostatic cancer and treated with radical prostatectomy between January 2008 and January 2013 were followed up until death or January 2018. According to biochemical reoccurrence,they were divided into the observation group（ with biochemical reoccurrence,n = 78） and the control group（ without biochemical reoccurrence,n = 202）. The peripheral blood of the two groups was collected before radical prostatectomy in order to observe SNPs in FokⅠ and TaqⅠ in VDR genes. The frequencies of alleles and genotype of the two groups were compared.Results The SNPs of FokⅠ and TaqⅠ in the two groups conformed with the Hardy-Weinberg genetic balance. The genotype and allele frequencies of FokⅠ differed significantly between the two groups（ P〉0.05）. With FF genotype-carrying patients as control,patients with the Ff or ff genotype were at higher risk of biochemical recurrence（ OR = 2.966,95% CI = 1. 389 - 6. 332; OR = 4. 590,95% CI = 2. 014 - 10. 463）,so were patients who carried allele f（ OR = 2.059,95%CI = 1.412 - 3.001）. The genotype and allele frequencies of Taq I were similar in the two groups（ P〉0.05）. Multivariate Cox analysis showed that FokⅠ genotype FF was an independent protective factor for biochemical recurrence in patients（ P〈0.05）.Conclusion SNPs of FokⅠ in VDR genes may be associated with biochemical recurrence of prostatic cancer after radical prostatectomy. Allele f may be a risk factor for biochemical recurrence,whereas the FF genotype may be a protective factor for biochemical recurrence.