Ferreira Arlindo, Alho Irina, Vendrell Inês, Melo Marta, Brás Raquel, Costa Ana Lúcia, Sousa Ana Rita, Mansinho André, Abreu Catarina, Pulido Catarina, Macedo Daniela, Pacheco Teresa, Correia Lurdes, Costa Luis, Casimiro Sandra
Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
Oncology Division, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisbon, Portugal.
Oncotarget. 2016 Jul 5;7(27):41380-41389. doi: 10.18632/oncotarget.9356.
Receptor activator of NF-kB (RANK) pathway regulates bone remodeling and is involved in breast cancer (BC) progression. Genetic polymorphisms affecting RANK-ligand (RANKL) and osteoprotegerin (OPG) have been previously associated with BC risk and bone metastasis (BM)-free survival, respectively. In this study we conducted a retrospective analysis of the association of five missense RANK SNPs with clinical characteristics and outcomes in BC patients with BM. SNP rs34945627 had an allelic frequency of 12.5% in BC patients, compared to 1.2% in the control group (P = 0.005). SNP rs34945627 was not associated with any clinicopathological characteristics, but patients presenting SNP rs34945627 had decreased disease-free survival (DFS) (log-rank P = 0.039, adjusted HR 2.29, 95% CI 1.04-5.08, P = 0.041), and overall survival (OS) (log-rank P = 0.019, adjusted HR 4.32, 95% CI 1.55-12.04, P = 0.005). No differences were observed regarding bone disease-free survival (log-rank P = 0.190, adjusted HR 1.68, 95% CI 0.78-3.66, P = 0.187), time to first skeletal-related event (log-rank P = 0.753, adjusted HR 1.28, 95% CI 1.42-3.84; P = 0.665), or time to bone progression (log-rank P = 0.618, adjusted HR 0.511, 95% CI 0.17-1.51; P = 0.233). Our analysis shows that RANK SNP rs34945627 has a high allelic frequency in patients with BC and BM, and is associated with decreased DFS and OS.
核因子-κB受体激活剂（RANK）通路调节骨重塑，并参与乳腺癌（BC）进展。影响RANK配体（RANKL）和骨保护素（OPG）的基因多态性先前分别与BC风险和无骨转移（BM）生存期相关。在本研究中，我们对5个错义RANK单核苷酸多态性（SNP）与BM的BC患者的临床特征及预后的相关性进行了回顾性分析。SNP rs34945627在BC患者中的等位基因频率为12.5%，而在对照组中为1.2%（P = 0.005）。SNP rs34945627与任何临床病理特征均无关联，但携带SNP rs34945627的患者无病生存期（DFS）缩短（对数秩检验P = 0.039，校正风险比2.29，95%置信区间1.04 - 5.08，P = 0.041），总生存期（OS）缩短（对数秩检验P = 0.019，校正风险比4.32，95%置信区间1.55 - 12.04，P = 0.005）。在无骨病生存期（对数秩检验P = 0.190，校正风险比1.68，95%置信区间0.78 - 3.66，P = 0.187）、首次骨相关事件发生时间（对数秩检验P = 0.753，校正风险比1.28，95%置信区间1.42 - 3.84；P = 0.665）或骨进展时间（对数秩检验P = 0.618，校正风险比0.511，95%置信区间0.17 - 1.51；P = 0.233）方面未观察到差异。我们的分析表明，RANK SNP rs34945627在伴有BM的BC患者中等位基因频率较高，且与DFS和OS降低相关。
