Geburtshilfe Frauenheilkd 2014; 74 - PO_Onko03_08
DOI: 10.1055/s-0034-1388372

Polymorphisms in the RANK/RANKL genes and their effect on bone specific prognosis in breast cancer patients

A Hein 1, CM Bayer 1, MG Schrauder 1, L Häberle 1, K Heusinger 1, R Strick 1, M Ruebner 1, MP Lux 1, SP Renner 1, R Schulz-Wendtland 2, AB Ekici 3, A Hartmann 4, MW Beckmann 1, PA Fasching 1
  • 1Universitätsklinikum Erlangen, Frauenklinik, Erlangen, Germany
  • 2Universitätsklinikum Erlangen, Radiologisches Institut, Erlangen, Germany
  • 3Universitätsklinikum Erlangen, Humangenetisches Institut, Erlangen, Germany
  • 4Universitätsklinikum Erlangen, Pathologisches Institut, Erlangen, Germany

The receptor activator of NF-κB (RANK) pathway is involved in bone health as well as breast cancer (BC) pathogenesis and progression. Whereas the therapeutic implication of this pathway is established for the treatment of osteoporosis and bone metastases, the application in adjuvant BC is currently investigated. As genetic variants in this pathway have been described to influence bone health, aim of this study was the prognostic relevance of genetic variants in RANK and RANKL.

Single nucleotide polymorphisms (SNPs) in RANK(L) (rs1054016/rs1805034/rs35211496) were genotyped and analyzed with regard to bone metastasis free survival (BMFS), disease free survival and overall survival for a retrospective cohort of 1251 patients. Cox proportional hazards models were fitted to examine the prognostic influence in addition to commonly established prognostic factors.

The SNP rs1054016 seems to influence BMFS. Patients with two minor alleles had a more favorable prognosis than patients with at least one common allele (HR 0,37 [95% CI: 0,17; 0,84]), whereas other outcome parameters remained unaffected. rs1805034 and rs35211496 had no prognostic relevance.

The effect of rs1054016 (RANKL) adds to the evidence, that the RANK pathway plays a role in BC pathogenesis and progression with respect to BMFS, emphasizing the connection between BC and bone health.