Department of Clinical Immunology, Laboratory of Clinical Immunogenetics and Pharmacogenetics, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland.
Department of Cancer Prevention and Therapy, Wroclaw Medical University, Wrocław, Poland.
Mol Carcinog. 2021 Feb;60(2):106-112. doi: 10.1002/mc.23272. Epub 2020 Dec 7.
Multiple myeloma (MM) is a heterogeneous bone marrow cancer characterized by proliferation of malignant plasma cells in the bone marrow. One of its major symptoms are hypercalcaemia and bone lesions, which may result in pathologic bone fractures. Receptor activator for nuclear factor κB (RANK) and its ligand, RANKL, are part of an activation pathway for osteoclasts and are thus responsible for bone resorption. Furthermore, RANKL expression is increased in multiple myeloma. In the present study, we investigated the role of single nucleotide polymorphisms (SNPs) in the genes coding for RANK (rs1805034, rs8086340), RANKL (rs7325635, rs7988338), and TACI (rs34562254), a receptor for osteoclast-derived pro-survival factors. The study involved 222 patients and 222 healthy individuals, and the analysis included disease susceptibility, survival, bone lesions, calcium levels, and vascular endothelial growth factor levels. Patients with allele RANK rs1805034 C had higher survival (p = .003). This relationship was especially evident in women (p = .006). Furthermore, allele rs1805034 C was associated with slightly lower median age at diagnosis (64.0 vs. 65.5, p = .008). Allele RANKL rs7325635 A correlated with lower progression-free survival (p = .027), and with lack of early progression (p = .023). Additionally, women with allele rs7325635 G were found to have higher calcium blood concentration (p = .040). Allele TACI rs34562254 A was more common in MM patients in more advanced stages (II and III stage International Staging System) at diagnosis (p = .017), and the SNP showed a slight trend towards association in a multivariate analysis (p = .084). Taken together, our results suggest that RANK rs1805034 and RANKL rs7325635 may have a role in MM development and progression.
多发性骨髓瘤（MM）是一种异质性骨髓癌，其特征是骨髓中恶性浆细胞的增殖。其主要症状之一是高钙血症和骨病变，这可能导致病理性骨折。核因子 κB 受体激活剂（RANK）及其配体 RANKL 是破骨细胞激活途径的一部分，因此负责骨吸收。此外，RANKL 在多发性骨髓瘤中的表达增加。在本研究中，我们研究了编码 RANK（rs1805034、rs8086340）、RANKL（rs7325635、rs7988338）和 TACI（rs34562254）的基因中的单核苷酸多态性（SNP）在疾病易感性、生存、骨病变、钙水平和血管内皮生长因子水平中的作用。该研究纳入了 222 例患者和 222 例健康对照，分析包括疾病易感性、生存、骨病变、钙水平和血管内皮生长因子水平。等位基因 RANK rs1805034 C 的患者具有更高的生存率（p=.003）。这种关系在女性中尤为明显（p=.006）。此外，等位基因 rs1805034 C 与较低的中位诊断年龄相关（64.0 岁与 65.5 岁，p=.008）。等位基因 RANKL rs7325635 A 与无进展生存期较短相关（p=.027），与早期无进展相关（p=.023）。此外，携带等位基因 rs7325635 G 的女性的血钙浓度更高（p=.040）。在诊断时处于更晚期（国际分期系统 II 期和 III 期）的 MM 患者中，等位基因 TACI rs34562254 A 更为常见（p=.017），在多变量分析中，该 SNP 也表现出轻微的关联趋势（p=.084）。综上所述，我们的结果表明 RANK rs1805034 和 RANKL rs7325635 可能在 MM 的发展和进展中发挥作用。
