Goričar Katja, Kovač Viljem, Jazbec Janez, Lamovec Janez, Dolžan Vita
Pharmacogenetics Laboratory, Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
Institute of Oncology Ljubljana, Ljubljana, Slovenia.
J Med Biochem. 2015 Apr;34(2):200-206. doi: 10.2478/jomb-2014-0031. Epub 2015 Mar 3.
DNA repair mechanisms are essential for maintaining genome stability, and genetic variability in DNA repair genes may contribute to cancer susceptibility. Our aim was to evaluate the influence of polymorphisms in the homologous recombination repair genes , , and on the risk for osteosarcoma.
In total, 79 osteosarcoma cases and 373 controls were genotyped for eight single nucleotide polymorphisms (SNPs) in , , and . Logistic regression was used to determine the association of these SNPs with risk for osteosarcoma.
None of the investigated SNPs was associated with risk for osteosarcoma in the whole cohort of patients, however, in patients diagnosed before the age of thirty years rs861539 C>T and rs1805794 G>C were associated with significantly decreased risk for osteosarcoma (=0.047, OR=0.54, 95% CI=0.30-0.99 and =0.036, OR=0.42, 95% CI=0.19-0.94, respectively). Moreover, in the carriers of a combination of polymorphic alleles in both SNPs risk for osteosarcoma was decreased even more significantly (=0.007). The risk for developing osteosarcoma was the lowest in patients with no wild-type alleles for both SNPs (=0.039, OR=0.31, 95% CI=0.10-0.94).
Our results suggest that polymorphisms in homologous recombination repair genes might contribute to risk for osteosarcoma in patients diagnosed below the age of thirty years.
DNA修复机制对于维持基因组稳定性至关重要，DNA修复基因中的遗传变异可能会增加患癌易感性。我们的目的是评估同源重组修复基因、和中的多态性对骨肉瘤风险的影响。
对79例骨肉瘤病例和373例对照进行了、和中8个单核苷酸多态性（SNP）的基因分型。采用逻辑回归分析确定这些SNP与骨肉瘤风险的相关性。
在整个患者队列中，所研究的SNP均与骨肉瘤风险无关。然而，在30岁之前确诊的患者中，rs861539 C>T和rs1805794 G>C与骨肉瘤风险显著降低相关（分别为=0.047，OR=0.54，95%CI=0.30-0.99和=0.036，OR=0.42，95%CI=0.19-0.94）。此外，在两个SNP中均携带多态性等位基因组合的携带者中，骨肉瘤风险降低更为显著（=0.007）。在两个SNP均无野生型等位基因的患者中，发生骨肉瘤的风险最低（=0.039，OR=0.31，95%CI=0.10-0.94）。
我们的结果表明，同源重组修复基因中的多态性可能会增加30岁以下确诊患者患骨肉瘤的风险。
