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治疗前维生素D水平和维生素D受体作为实体瘤患儿发生情况和总生存的潜在预测指标——一项单机构试点研究

Pre-treatment VD levels and VDR receptors as potential predictors of occurrence and overall survival in paediatric patients with solid tumours-a single institution pilot study.

作者信息

Bienertová-Vašků Julie, Drábová Klára, Zlámal Filip, Tomandl Josef, Kýr Michal, Šplíchal Zbyněk, Štěrba Jaroslav

机构信息

Department of Pathological Physiology, Faculty of Medicine, Masaryk University, Kamenice 5, Building A18, 625 00, Brno, Czech Republic.

Department of Paediatric Oncology, University Hospital Brno, Černopolní 22, Brno, 613 00, Czech Republic.

出版信息

Tumour Biol. 2016 Jul;37(7):9209-19. doi: 10.1007/s13277-016-4820-9. Epub 2016 Jan 14.

DOI:10.1007/s13277-016-4820-9
PMID:26768618
Abstract

Recently, vitamin D has been recognized as an important player in the immune system, and multiple studies suggested its involvement in cancer, too. The aims of this study were to investigate selected single nucleotide polymorphisms (SNPs) in the VDR gene, BsmI (rs1544410; A > G), FokI (rs 2228570; C > T), TaqI (rs731236; T > C), ApaI (rs 7975232; C > T) and Cdx-2 (rs11568820; A > G), and to evaluate their possible predictive role for outcomes in patients with paediatric solid tumours. A total of 111 children with paediatric solid tumours were enrolled at the Department of Paediatric Oncology, University Hospital Brno (Brno, Czech Republic) along with a control population of 787 adults; all study subjects were available for genotyping of selected SNPs, and the prediagnostic levels of 25-hydroxycholecalciferol (25(OH)D3) and 1,25-dihydroxycholecalciferol (1,25(OH)2D3) were measured in the cases, too. In FokI, the heterozygote CT genotype was weakly associated with a decreased risk of paediatric solid cancer occurrence 0.82 (0.53-1.28), while the CC genotype was associated with a decreased risk of 0.58 (0.30-1.09), p = 0.09. The 1,25(OH)2D3 prediagnostic levels were indicative of the overall survival in the cases (β = -0.012, HR 0.988, 95 % CI (0.978-0.998), while higher prediagnostic levels of 1,25(OH)2D3 were associated with a statistically significant increase in overall mortality. We observed multiple effects of the alleles of the investigated polymorphisms and of 1,25(OH)2D3 on overall survival, regardless of the underlying disease.

摘要

最近,维生素D已被公认为免疫系统中的重要角色,多项研究表明它也与癌症有关。本研究的目的是调查维生素D受体(VDR)基因中的特定单核苷酸多态性(SNP),即BsmI(rs1544410;A>G)、FokI(rs2228570;C>T)、TaqI(rs731236;T>C)、ApaI(rs7975232;C>T)和Cdx-2(rs11568820;A>G),并评估它们对小儿实体瘤患者预后的可能预测作用。捷克布尔诺大学医院儿科肿瘤学系共招募了111名患有小儿实体瘤的儿童以及787名成年对照人群;所有研究对象均进行了所选SNP的基因分型,并且也测量了病例组中25-羟基胆钙化醇(25(OH)D3)和1,25-二羟基胆钙化醇(1,25(OH)2D3)的诊断前水平。在FokI中,杂合子CT基因型与小儿实体癌发生风险降低呈弱相关,风险比为0.82(0.53 - 1.28),而CC基因型与风险降低呈相关,风险比为0.58(0.30 - 1.09),p = 0.09。1,25(OH)2D3的诊断前水平可指示病例组的总生存期(β = -0.012,风险比0.988,95%置信区间(0.978 - 0.998)),而较高的1,25(OH)2D3诊断前水平与总死亡率的统计学显著增加相关。我们观察到所研究的多态性等位基因和1,25(OH)2D3对总生存期有多种影响,与潜在疾病无关。

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