title: The prognostic role of RANK SNP rs34945627 in breast cancer patients with bone metastases.
abstract: 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.
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.|Oncology Division, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisbon, Portugal.
authors.forename: Arlindo
authors.initials: A
authors.lastname: Ferreira
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
authors.forename: Irina
authors.initials: I
authors.lastname: Alho
authors.affiliation: Oncology Division, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisbon, Portugal.
authors.forename: Inês
authors.initials: I
authors.lastname: Vendrell
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
authors.forename: Marta
authors.initials: M
authors.lastname: Melo
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
authors.forename: Raquel
authors.initials: R
authors.lastname: Brás
authors.affiliation: Oncology Division, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisbon, Portugal.
authors.forename: Ana Lúcia
authors.initials: AL
authors.lastname: Costa
authors.affiliation: Oncology Division, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisbon, Portugal.
authors.forename: Ana Rita
authors.initials: AR
authors.lastname: Sousa
authors.affiliation: Oncology Division, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisbon, Portugal.
authors.forename: André
authors.initials: A
authors.lastname: Mansinho
authors.affiliation: Oncology Division, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisbon, Portugal.
authors.forename: Catarina
authors.initials: C
authors.lastname: Abreu
authors.affiliation: Oncology Division, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisbon, Portugal.
authors.forename: Catarina
authors.initials: C
authors.lastname: Pulido
authors.affiliation: Oncology Division, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisbon, Portugal.
authors.forename: Daniela
authors.initials: D
authors.lastname: Macedo
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.|Oncology Division, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisbon, Portugal.
authors.forename: Teresa
authors.initials: T
authors.lastname: Pacheco
authors.affiliation: Pathology Division, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisbon, Portugal.
authors.forename: Lurdes
authors.initials: L
authors.lastname: Correia
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.|Oncology Division, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisbon, Portugal.
authors.forename: Luis
authors.initials: L
authors.lastname: Costa
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
authors.forename: Sandra
authors.initials: S
authors.lastname: Casimiro
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics; D001859:Bone Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000556:secondary*; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000235:genetics*; D012189:Retrospective Studies; D012307:Risk Factors; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; D053246:Receptor Activator of Nuclear Factor-kappa B; C505686:TNFRSF11A protein, human
keywords: RANK/RANKL pathway; bone metastases; breast cancer; prognostic factor; single nucleotide polymorphism