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.

中文翻译：

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RANK和RANKL基因多态性与多发性骨髓瘤生存率和钙水平的关系

多发性骨髓瘤（MM）是一种异质性骨髓癌，其特征在于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骼损伤，可能导致病理性骨折。核因子κB（RANK）及其配体RANKL的受体激活剂是破骨细胞激活途径的一部分，因此负责骨吸收。此外，在多发性骨髓瘤中RANKL表达增加。在本研究中，我们研究了单核苷酸多态性（SNP）在编码RANK（rs1805034，rs8086340），RANKL（rs7325635，rs7988338）和TACI（rs34562254）的基因中的作用，破骨细胞源性生存前体受体因素。该研究涉及222名患者和222名健康个体，分析包括疾病易感性，生存率，骨病变，钙水平和血管内皮生长因子水平。RANK等位基因患者rs1805034C具有更高的生存率（p  = 0.003）。这种关系在女性中尤为明显（p  = .006）。此外，等位基因rs1805034 C与诊断时的中位年龄略低有关（64.0 vs. 65.5，p  = .008）。等位基因RANKL rs7325635 A与较低的无进展生存期（p  = .027）和缺乏早期进展相关（p  = .023）。此外，发现具有等位基因rs7325635 G的女性血钙浓度较高（p  = .040）。等位基因TACI rs34562254 A在诊断较高阶段（II和III期国际分期系统）的MM患者中更为常见（p  = .017），而在多变量分析中，SNP表现出轻微的趋向趋势（p  = .084）。两者合计，我们的结果表明RANK rs1805034和RANKL rs7325635可能在MM的发展和进程中起作用。