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Open Access Research article

Genetic polymorphism of the OPG gene associated with breast cancer

Jasmin Teresa Ney16*, Ingolf Juhasz-Boess1, Frank Gruenhage2, Stefan Graeber3, Rainer Maria Bohle4, Michael Pfreundschuh5, Erich Franz Solomayer1 and Gunter Assmann5

Author affiliations

1 Gynecology, Obstetrics and Reproductive Medicine, University Medical School of Saarland, 66421, Homburg/Saar, Saarland, Germany

2 Internal Medicine II, University Medical School of Saarland, 66421, Homburg/Saar, Saarland, Germany

3 Institute of Medical Biometry, Epidemiology and Medical Informatics, Saarland University, 66421, Homburg/Saar, Saarland, Germany

4 General and Surgical Pathology, University Medical School of Saarland, 66421, Homburg/Saar, Saarland, Germany

5 Internal Medicine I, José-Carreras-Center for Immuno- and Gene Therapy, University Medical School of Saarland, 66421, Homburg/Saar, Saarland, Germany

6 Universitätsklinikum des Saarlandes, Klinik für Frauenheilkunde, Geburtshilfe und Reproduktionsmedizin, Kirrbergerstr, 66421, Homburg/Saar, Germany

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Citation and License

BMC Cancer 2013, 13:40  doi:10.1186/1471-2407-13-40

Published: 31 January 2013



The receptor activator of NF-κB (RANK), its ligand (RANKL) and osteoprotegerin (OPG) have been reported to play a role in the pathophysiological bone turnover and in the pathogenesis of breast cancer. Based on this we investigated the role of single nucleotide polymorphisms (SNPs) within RANK, RANKL and OPG and their possible association to breast cancer risk.


Genomic DNA was obtained from Caucasian participants consisting of 307 female breast cancer patients and 396 gender-matched healthy controls. We studied seven SNPs in the genes of OPG (rs3102735, rs2073618), RANK (rs1805034, rs35211496) and RANKL (rs9533156, rs2277438, rs1054016) using TaqMan genotyping assays. Statistical analyses were performed using the χ2-tests for 2 x 2 and 2 x 3 tables.


The allelic frequencies (OR: 1.508 CI: 1.127-2.018, p=0.006) and the genotype distribution (p=0.019) of the OPG SNP rs3102735 differed significantly between breast cancer patients and healthy controls. The minor allele C and the corresponding homo- and heterozygous genotypes are more common in breast cancer patients (minor allele C: 18.4% vs. 13.0%; genotype CC: 3.3% vs. 1.3%; genotype CT: 30.3% vs. 23.5%). No significantly changed risk was detected in the other investigated SNPs. Additional analysis showed significant differences when comparing patients with invasive vs. non-invasive tumors (OPG rs2073618) as well as in terms of tumor localization (RANK rs35211496) and body mass index (RANKL rs9533156 and rs1054016).


This is the first study reporting a significant association of the SNP rs3102735 (OPG) with the susceptibility to develop breast cancer in the Caucasian population.

Breast cancer; Case control study; OPG; Polymorphism; RANK; RANKL; rs3102735