Association Of SLC7A7Genetic Polymorphism With Glioma Susceptibility And Prognosic Significance Of SLC7A7Overexpression In Patients With Glioblastoma

Part I Association of SLC7A7Polymorphism with Glioma Susceptibility in a Chinese Han PopulationObjective:We aimed to explore the association of SLC7A7polymorphism with glioma genetic susucetibility in a Chinese Han population.Methods:The study was based on the case-control retrospective method. Briefly, patients with histologically confirmed glioma were consecutively recruited between August2005and August2010from Department of Neurosurgery at Huashan Hospital, Fudan University (Shanghai, China). The793cancer-free controls were randomLy selected from visitors to the health examination clinic for a general check-up at the same hospital during the same study period.Then leucocyte samples were collected from all participanted. All the control subjects were frequency matched to the cases by age, sex and residential area (urban or rural). The39tagging SNPs on SLC7A7harboring～46kb of genomic DNA were genotyped using the Illumina SNP genotyping BeadLab platform (Illumina, Inc., San Diego, CA) at Chinese National Human Genome Center and were analysed on the association with disease susceptibility by SPSS and Haploview software.Results:Allele frequencies6of the39genotyped tag SNPs were significantly different between cases and controls as revealed in single locus analysis (P=0.017, P=0.003, P=0.047, P=0.021, P=0.028, P=0.046). Increasing risk for GBM was associated with the variant genotype of rs12433985(adjusted OR=1.43;95%CI=1.08-1.91) and rs12433985(adjusted OR=1.78;95%CI=1.20-2.64) in a dominant model. Similar trend was observed for rsl2433985(adjusted OR=1.36;95%CI=1.06-1.73) in non-GBMs. Under recessive model, rsl2888930can significantly increase GBM risk (adjuested OR=1.59;95%CI=1.06-2.39), while rs12436190can increase risk for non-GBM (adjuested OR=1.43;95%CI=1.06-1.9). The risk of rs12436190C/C,rs12433985A/G+AA, rs12436190A/A were more pronounced among males (P=0.018, P=0.004, P=0.006) and the risk of rs12433985A/G, rs12436190A/A, rs12884337C/C were more pronounced among cases<47years old (P=0.025, P=0.016, P=0.04). Haplotype analysis showed that the hyplotype type AG and GG (rs11568429-rs12433985) were associated with decreased risk for glioma (global P=0.014, adjusted OR=0.77,95%CI=0.65-0.92; OR=0.82,95%CI=0.69-0.98, respectively).Conclusion:Taken together, these results suggest that SLC7A7polymorphism/haplotypes may contribute to genetic susceptibility of glioma. Part II Assosiation of SLC7A7Overexpression with Poor Progression-free and Overall Survival of GBM PatientsObjective:In the study, we tried to explore whether overexpression of SLC7A7gene was associated with progression-free and overall survival of glioblastoma patients.Methods:A total of119patients with pathologically confirmed GBM on WHO new standard and16normal controls were recruited for this study. The expression of SLC7A7in GBM and normal tissues was evaluated by immunohistochemistry in tissue microarrays and quantitative real-time PCR.Results:Immunohistochemistry analysis showed that SLC7A7expression was rarely detected in normal controls but significant increase of SLC7A7expression in GBMs tissues was observed (P<0.01). Quantitative real-time PCR revealed that SLC7A7mRNA transcription level was significantly elevated in GBMs specimens compared to that of normal controls (P=0.028, fold change=3.53). In the multivariate analysis by Kaplan-Meier method and Cox’s proportional hazards model, we found that overexpression of SLC7A7was significant and independent indicators for predicting poor prognosis.Conclusion:Our results suggest for the first time that overexpression of SLC7A7is correlated with worse outcomes in patients with GBM. SLC7A7plays a critical role in GBM carcinogenesis and may be a potential prognosis predictor of GBM.