Introduction: The association of single-nucleotide polymorphisms at X-ray repair cross-complementing group-1 (XRCC1) with osteosarcoma (OS) development has not been fully clear to date. The aim of the present study is to evaluate the association of XRCC1 polymorphisms with risk, clinicopathologic features, and prognosis in Chinese OS patients.
Methods: A total of 146 patients with primary OS and 248 age- and gender-matched controls were included in the present study. The frequencies of four XRCC1 polymorphisms (rs25487, rs1799782, rs25489, and rs3213245) were determined between OS patients and controls. The association of XRCC1 polymorphism with clinicopathologic characteristics, prognosis, and XRCC1 expression was further evaluated.
Results: Compared with TT genotype, individuals carrying the minor C allele (TC+ CC) of rs3213245 had significantly increased risk of OS development (OR =1.83, 95% CI 1.14–3.00). OS patients carrying TC genotype and C allele at rs3213245 were more likely to be with larger tumor size and metastasis. Survival analysis demonstrated that OS patients carrying C allele (TC + CC) at rs3213245 had shorter survival time than those with TT genotype. The T to C substitution at rs3213245 could decrease XRCC1  gene transcriptional activity in vitro. XRCC1 mRNA and protein expression levels were lower in OS patients carrying TC or CC genotype at rs3213245. Besides, no significant association of rs25487, rs1799782, and rs25489 with OS was observed.
Conclusion: In conclusion, these findings revealed that XRCC1 rs3213245 polymorphism was associated with increased risk of OS, which could affect XRCC1 expression in vitro and in vivo.
Keywords: osteosarcoma, XRCC1, polymorphism, prognosis