Department of Dermatology, Venereology, and Allergology, Georg August University Göttingen, Robert-Koch-Strasse 40, 37075, Göttingen, Germany.
Arch Dermatol Res. 2012 Jul;304(5):353-61. doi: 10.1007/s00403-012-1243-3. Epub 2012 May 11.
Melanoma is one of the most aggressive human cancers. The vitamin D system contributes to the pathogenesis and prognosis of malignancies including cutaneous melanoma. An expression of the vitamin D receptor (VDR) and an anti-proliferative effect of vitamin D in melanocytes and melanoma cells have been shown in vitro. Studies examining associations of polymorphisms in genes coding for vitamin D metabolism-related proteins (1α-hydroxylase [CYP27B1], 1,25(OH)(2)D-24hydroxylase [CYP24A1], vitamin D-binding protein [VDBP]) and cancer risk are scarce, especially with respect to melanoma. Mainly VDR polymorphisms regarding melanoma risk and prognosis were examined although other vitamin D metabolism-related genes may also be crucial. In our hospital-based case-control study including 305 melanoma patients and 370 healthy controls single nucleotide polymorphisms in the genes CYP27B1 (rs4646536), CYP24A1 (rs927650), VDBP (rs1155563, rs7041), and VDR (rs757343, rs731236, rs2107301, rs7975232) were analyzed for their association with melanoma risk and prognosis. Except VDR rs731236 and VDR rs2107301, the other six polymorphisms have not been analyzed regarding melanoma before. To further improve the prevention as well as the treatment of melanoma, it is important to identify further genetic markers for melanoma risk as well as prognosis in addition to the crude phenotypic, demographic, and environmental markers used in the clinic today. A panel of genetic risk markers could help to better identify individuals at risk for melanoma development or worse prognosis. We, however, found that none of the polymorphisms tested was associated with melanoma risk as well as prognosis in logistic and linear regression models in our study population.
黑色素瘤是最具侵袭性的人类癌症之一。维生素 D 系统有助于包括皮肤黑色素瘤在内的恶性肿瘤的发病机制和预后。已经在体外证明了维生素 D 受体 (VDR) 的表达和维生素 D 在黑素细胞和黑色素瘤细胞中的抗增殖作用。研究检查了编码维生素 D 代谢相关蛋白(1α-羟化酶 [CYP27B1]、1,25(OH)(2)D-24 羟化酶 [CYP24A1]、维生素 D 结合蛋白 [VDBP])的基因多态性与癌症风险之间的关联的研究很少,特别是关于黑色素瘤。虽然其他维生素 D 代谢相关基因也可能至关重要,但主要检查了 VDR 多态性与黑色素瘤风险和预后的关系。在我们的基于医院的病例对照研究中,包括 305 名黑色素瘤患者和 370 名健康对照者,分析了 CYP27B1(rs4646536)、CYP24A1(rs927650)、VDBP(rs1155563、rs7041)和 VDR(rs757343、rs731236、rs2107301、rs7975232)基因中的单核苷酸多态性与黑色素瘤风险和预后的关系。除了 VDR rs731236 和 VDR rs2107301 之外,以前没有分析过其他六个多态性与黑色素瘤有关。除了今天临床使用的粗略表型、人口统计学和环境标志物外,为了进一步改善黑色素瘤的预防和治疗,识别除黑色素瘤风险和预后以外的进一步遗传标志物非常重要。一组遗传风险标志物可以帮助更好地识别黑色素瘤发展或预后较差的个体。然而,在我们的研究人群中,我们发现逻辑回归和线性回归模型中测试的多态性均与黑色素瘤风险和预后无关。