The prognostic role of RANK SNP rs34945627 in breast cancer patients with bone metastases
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Arlindo Ferreira1,2,*, Irina Alho1,*, Inês Vendrell2, Marta Melo1, Raquel Brás1, Ana Lúcia Costa2, Ana Rita Sousa2, André Mansinho2, Catarina Abreu2, Catarina Pulido2, Daniela Macedo2, Teresa Pacheco1,2, Lurdes Correia3, Luis Costa1,2, Sandra Casimiro1
1Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
2Oncology Division, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisbon, Portugal
3Pathology Division, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisbon, Portugal
*These authors contributed equally to this work
Sandra Casimiro, email: email@example.com
Luis Costa, email: firstname.lastname@example.org
Keywords: breast cancer, bone metastases, RANK/RANKL pathway, single nucleotide polymorphism, prognostic factor
Received: March 02, 2016 Accepted: March 31, 2016 Published: May 13, 2016
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.
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