Determination of Rank, Rankl and Opg Gene Polymorphisms in Triple-Negative Breast Cancer Patients and Investigation of its Effect on Bone Metastasis

Abstract

Objective: Triple negative breast cancer (TNBC) is a sub-type of breast cancer with the worst prognosis and highest risk of mortality. Bone metastasisis the most common metastasis type among women with breast cancer. RANK and OPG, are the members of the family of tumor necrosis factor(TNF), which is effective on osteoblastic and osteoclastic mechanisms. RANKL, interacts with RANK and leads to bone resorption, whereas it inhibitsbone destruction when it interacts with OPG.Methods: In this study, we investigated the polymorphisms of RANK, RANKL and OPG genes and their effects on bone metastasis in 45 patients withtriple negative breast cancer and 30 healthy controls, using PCR, RFLP and agarose gel electrophoresis techniques.Results: The RANKL genotype and allele distribution analysis revealed a significantly increased CC genotype incidence in patients with TNBC andbone metastasis (p=0.011) and in those without bone metastasis (p=0.004) compared to the control group. The OPG genotype and allele distributionanalysis revealed significantly increased C allele incidence in patients with TNBC and bone metastasis (p=0.004) compared to the control group.Likewise, the CC genotype (p=0.001) and C allele incidences (p=0.001) were observed to be significantly increased in patients with TNBC comparedto healthy controls.Conclusion: This study is one of the first studies investigating all three RANK/RANKL/OPG gene polymorphisms and the relationship between breastcancer and bone metastasis in our country. We believe that our study will shed light onto further studies to be conducted on triple negative breast cancer and bone metastasis.