ABSTRACT:
BACKGROUND:
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.
METHODS:
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.
RESULTS:
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).
CONCLUSIONS:
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.
Source: Genetic polymorphism of the
OPG gene associated with breast cancer. Ney JT (jasmin.ney@uks.eu) Juhasz-Boess I,
Gruenhage F, Graeber S, Bohle RM, Pfreundschuh M, Solomayer EF, Assmann G. BMC
Cancer. 2013 Jan 31;13:40.
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