The effects of common variants in MDM2 and GNRH2 genes on the risk and survival of osteosarcoma in Han populations from Northwest China

Weilou Feng,Wei Huang,Zhi Wang,Kun Zhang,Yangjun Zhu,Dongxu Feng

doi:10.1038/s41598-020-72995-4

Weilou Feng, Wei Huang + Show 4 more

Open Access

https://doi.org/10.1038/s41598-020-72995-4

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Abstract

Accumulating evidence has shown that both MDM2 and GNRH2 might be related to Osteosarcoma (OS) susceptibility. The study aimed to evaluate the effects of common variants in MDM2 and GNRH2 genes on the risk and survival of osteosarcoma in Han populations from Northwest China. In the study, we recruited 2292 subjects including 596 OS patients and 1696 healthy controls and genotyped 16 selected tag SNPs (6 from GNRH2 and 10 from MDM2). Genetic association analyses were performed at the genotypic and allelic levels. Survival curves were made for OS patients with different genotypes. Two SNPs, rs1690916 (MDM2, P = 0.0002) and rs3761243 (GNRH2, P = 0.0004), were identified to be significantly associated with OS risk. Moreover, SNP rs3761243 was strongly associated with pathological fracture (P = 2.61 × 10–14), metastasis (P < 2.2 × 10–16), and Enneking stage (P < 2.2 × 10–16) in the OS group. Furthermore, survival curves based on different genotypes of SNP rs3761243 were found to be significantly different (P = 0.0003), suggesting increased risk with more copies of C alleles. Our results provide supportive evidence for genetic associations of MDM2 and GNRH2 genes with susceptibility to OS, and for the positive correlation of SNP rs3761243 in GNRH2 with the survival status of OS patients in Han populations from Northwest China.

Highlights

Accumulating evidence has shown that both MDM2 and GNRH2 might be related to Osteosarcoma (OS) susceptibility
Additional evidence has been reported suggesting that the single nucleotide polymorphism (SNP) rs16909916 located in the 3′ untranslated region of MDM2 is associated with susceptibility to OS in Europeans[8,9]
In order to examine the functional consequence of the associated SNPs, we investigated the potential expression quantitative trait loci signals of the significant SNPs using data obtained from the GTEx d atabase[17]