Association of genetic variants in the retinoblastoma binding protein 6 gene with the risk of glioma: a case-control study in a Chinese Han population

Object: The retinoblastoma binding protein 6 (RBBP6) gene plays an important role in the induction of apoptosis and regulation of the cell cycle, and interacts with both p53 and retinoblastoma protein in carcinogenesis. Recently, many studies investigating the function of the RBBP6 gene, including its roles in lung cancer and breast cancer, have been reported. However, the association between RBBP6 variants and glioma was unknown. Therefore, to uncover the association between single nucleotide polymorphisms (SNPs) of RBBP6 and glioma, a hospital-based case-control study was performed in a Chinese Han population.

Methods: Ten common tagging SNPs of the RBBP6 gene (covering 100% of all SNPs) were genotyped with the Sequenom MassARRY iPLEX platform, including 992 cases and 1008 controls, according to the HapMap database based on a pairwise linkage disequilibrium r(2) threshold of 0.8, minor allele frequency of 0.05, and Hardy-Weinberg equilibrium of 0.05.

Results: The authors found that 4 SNPs were significantly associated with glioma (rs2033214, p = 0.013, adjusted OR 2.46, 95% CI 1.18-5.14; rs11860248, p = 8.64 × 10-(6), adjusted OR 1.59, 95% CI 1.23-2.05; rs9933544, p = 3.65 × 10(-4), adjusted OR 1.39, 95% CI 1.13-1.87; rs13332653, p = 0.004, adjusted OR 1.49, 95% CI 1.14-1.95). Stratification analyses revealed that rs2033214 was only significantly associated with low-grade gliomas; rs9933544 and rs13332653 were only significantly associated with glioblastoma multiforme; and rs11860248 was significantly associated with both low-grade gliomas and glioblastoma multiforme, compared with the common wild-type homozygous genotype. Further stratified analysis revealed that rs11860248 was more pronounced in certain subgroups: adults, males, histological types, and family history of cancer. What's more, the haplotype and diplotype analyses consistently revealed that the subjects carrying 1 copy of haplotype CCGCC had a 53% increased glioma risk compared with their corresponding noncarriers (p = 0.018, adjusted OR 1.53, 95% CI 1.08-2.17).

Conclusions: The authors' results suggested that RBBP6 gene variants are associated with glioma and contribute to glioma susceptibility, which was first reported elsewhere. Individuals with the so-called risk alleles might have an increased risk of glioma. These results might provide new insight into the occurrence of glioma.