Genetic polymorphism of the OPG gene associated with breast cancer.
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.
Gynecology, Obstetrics and Reproductive Medicine, University Medical School of Saarland, 66421, Homburg/Saar, Saarland, Germany. jasmin.ney@uks.eu
Jasmin Teresa
JT
Ney
Ingolf
I
Juhasz-Boess
Frank
F
Gruenhage
Stefan
S
Graeber
Rainer Maria
RM
Bohle
Michael
M
Pfreundschuh
Erich Franz
EF
Solomayer
Gunter
G
Assmann
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000208:ethnology / Q000235:genetics*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005858:Germany / Q000453:epidemiology; D006801:Humans; D008875:Middle Aged; D016017:Odds Ratio; D053244:Osteoprotegerin / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D053245:RANK Ligand / Q000235:genetics; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000235:genetics; D018570:Risk Assessment; D012307:Risk Factors; D044465:White People / Q000235:genetics; D055815:Young Adult
D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human