Halsall John A, Osborne Joy E, Epstein Michael P, Pringle James H, Hutchinson Peter E
Department of Cancer Studies and Molecular Medicine; University of Leicester; Leicester, UK.
Dermatoendocrinol. 2009 Jan;1(1):54-7. doi: 10.4161/derm.1.1.7674.
The A allele of the A-1012G (rs4516035) vitamin D receptor (VDR) promoter polymorphism is associated with increased susceptibility and worsened outcome in malignant melanoma (MM). The A allele contains a GATA-3 binding site. There is a second polymorphism in the same promoter region, G-1520C (rs7139166), and there is potential for another GATA binding site in the G allele. Here, we tested the hypothesis that the G(-1520)A(-1012) haplotype might be a greater risk factor for MM than A-1012 alone. The A allele of A-1012G was preferentially linked to G of G-1520C and was more frequent in MM patients (p = 0.011) but G of G-1520C was not (p = 0.756). The CA haplotype was a very significant risk factor for MM (p = 0.0001) while the CG haplotype was protective (p = 0.014, combined model p = 0.00002). There was no effect of GA haplotype (p = 0.931), suggesting that that the difference in frequencies of the A allele between patients and controls was accounted for by the differences in frequencies of the CA haplotype. The A allele of A-1012G was more frequent in patients with metastasis (p = 0.054) than MM patients without metastasis, as was the G allele of G-1520C (p = 0.028). The GA haplotype was more frequent in patients with metastasis (p = 0.015), while frequencies of CA were similar. We suggest that the different roles of the A allele of A-1012G in susceptibility and metastasis risk may be a function of the availability of transcription factors in the differing cellular backgrounds related to susceptibility and progression of MM.
维生素D受体（VDR）启动子多态性A-1012G（rs4516035）的A等位基因与恶性黑色素瘤（MM）易感性增加及预后恶化相关。A等位基因包含一个GATA-3结合位点。在同一启动子区域存在另一个多态性G-1520C（rs7139166），且G等位基因中存在另一个GATA结合位点的可能性。在此，我们检验了这样一个假设，即G（-1520）A（-1012）单倍型可能比单独的A-1012是MM更大的风险因素。A-1012G的A等位基因优先与G-1520C的G连锁，且在MM患者中更常见（p = 0.011），但G-1520C的G并非如此（p = 0.756）。CA单倍型是MM的一个非常显著的风险因素（p = 0.0001），而CG单倍型具有保护作用（p = 0.014，联合模型p = 0.00002）。GA单倍型无影响（p = 0.931），这表明患者与对照之间A等位基因频率的差异是由CA单倍型频率的差异所致。A-1012G的A等位基因在有转移的患者中（p = 0.054）比无转移的MM患者更常见，G-1520C的G等位基因也是如此（p = 0.028）。GA单倍型在有转移的患者中更常见（p = 0.015），而CA的频率相似。我们认为，A-1012G的A等位基因在易感性和转移风险中不同的作用可能是与MM易感性和进展相关的不同细胞背景中转录因子可用性的一个函数。
