RAD52 Genetic Variants And Leukocyte Telomere Length-Related Genetic Variants Contribute To Risk Of Glioma In A Chinese Population

As a group of malignant tumors with a very poor prognosis, glioma accounts for approximately 80% of central nervous system cancer. We design the case-control study system; research the relationship between the RAD52 single nucleotide Polymorphisms and leukocyte telomere length (LTL)-related genetic variants and susceptibility of glioma.We investigated five single nucleotide polymorphisms (SNPs) of RAD52 (rs1051669, rs10774474, rs11571378, rs7963551 and rs6489769), logistic regression was used to estimate Odds ratios (OR) and 95% confidence intervals (CIs). We found that only the RAD52 rs7963551 SNP was significantly associated with glioma risk, with the odds of having the rs7963551 AC or CC genotype in patients was 0.49 (95% CI= 0.37-0.65, P = 9.29×10-6) or 0.39 (95% CI= 0.18-0.81, P= 0.012)compared with the AA genotype. Stratified analysis clarifies between glioma and rs7963551 SNP with a statistically significant relationship, both in astrocytomas (P= 6.3×10-6) or oligoastrocytic tumors (P= 0.002).Previous found that human peripheral blood leukocytes with shorter telomere length had the high incidence of certain cancers in European populations. Studies found that two SNPs 14q21 rs398652 and Ip34.2 rs621559 were significantly associated with leukocyte telomere length with genome-wide association studies (GWAS) in caucasion. Our previous data found that LTL-related SNPs (rs398652 on 14q21 and rs621559 on 1p34.2) were associated with the risk of esophageal squamous cell carcinoma in Chinese. Therefore, we examined if these genetic variants have impact on the genetic susceptibility of glioma in Chinese. We analyzed 404 cases of glioma and 820 matched normal controls, we found that subjects having the 1p34.2 rs621559 AG or GG genotype had an OR of 1.82 (95% CI= 1.07-3.09, P= 0.026) or 2.12 (95% CI= 1.26-3.56, P= 0.005) for developing glioma, compared with subjects having the rs621559 AA genotype. Similarly, the 14q21 rs398652 AG or GG genotype was associated with increased glioma risk (OR= 1.39,95% CI= 1.07-1.80, P = 0.012; OR= 1.52,95% CI= 1.04-2.20, P= 0.029) compared to AA genotype. In all, our results highlight the possible role of telomere in glioma carcinogenesis.Our results show that RAD52 rs7963551 as well as LTL-related SNPs rs621559 and rs398652 were associated with glioma risk.