Genetic polymorphism of the <it>OPG</it> gene associated with breast cancer

<p>Abstract</p> <p>Background</p> <p>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 <it>RANK</it>, <it>RANKL</it> and <it>OPG</it> and their possible association to breast cancer risk.</p> <p>Methods</p> <p>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 <it>OPG</it> (rs3102735, rs2073618), <it>RANK</it> (rs1805034, rs35211496) and <it>RANKL</it> (rs9533156, rs2277438, rs1054016) using TaqMan genotyping assays. Statistical analyses were performed using the χ²-tests for 2 x 2 and 2 x 3 tables.</p> <p>Results</p> <p>The allelic frequencies (OR: 1.508 CI: 1.127-2.018, p=0.006) and the genotype distribution (p=0.019) of the <it>OPG</it> 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 (<it>OPG</it> rs2073618) as well as in terms of tumor localization (<it>RANK</it> rs35211496) and body mass index (<it>RANKL</it> rs9533156 and rs1054016).</p> <p>Conclusions</p> <p>This is the first study reporting a significant association of the SNP rs3102735 (<it>OPG</it>) with the susceptibility to develop breast cancer in the Caucasian population.</p