| The incidence of glioma has been increasing significantly in the last two decadesin China, and glioma is the fourth cause of cancer-related deaths in most countries. Awide diversity of genetic damage induced by endogenous metabolites and exogenoushazards, such as exposure to ultraviolet, ionizing radiation, and chemical carcinogens,may contribute to the etiology of glioma. However, the exact molecular mechanismsunderlying genetic susceptibility to glioma are still under intensive investigation.Many studies have suggested that environmental and genetic factors may playimportant roles. ROS/RNS directly or indirectly with numerous molecules, whoseloss of function mutations can result in the destruction of tumor suppression functionsand genome instability in the brain. Oxidative stress in particular, may be one of theimportant host responses and therefore may contribute to tumor promotion andprogression. So, it is urgent to find out glioma etiology and take effective preventionmeasures. To reach this target, a hospital-based molecular epidemiological study onglioma was conducted in Jiangsu Province. PartⅠ A Case-control Study on Functional Variants in theSOD Gene are Associated with an Increased Risk of GliomaGlioma is the most common form of primary brain tumour in adults andgenerally yields a very poor prognosis. The oxidative stress mechanism is ofparticular interest in glioma, given the high rate of oxygen metabolism in the brain.Studies have showed the in vivo ability of SOD to regulate a variety of cellularfunctions in tumor cells. Potential links between the antioxidant genespolymorphisms and glioma risk are unknown. To test the hypothesis that SODpolymorphisms play an important role in the etiology of glioma in Chinesepopulations, we therefore investigated the association between the antioxidant genespolymorphisms and glioma risk. In the current study, we tested the hypothesis thatcommon non-synonymous polymorphisms in SOD are associated with gliomasusceptibility in a case-control study of400patients with incident glioma and400frequency-matched cancer-free controls in Chinese people. We found that the SOD2Val16Ala variant genotypes (16Val/Ala and16Ala/Ala) and SOD3Thr58Ala variantgenotypes (58Thr/Ala and58Ala/Ala) were associated with a significantly increaseglioma risk, compared with their wild-type homozygotes, respectively.Logistic regression analysis revealed that the SOD2rs4880CC and CT variantgenotypes were associated with increased risks for glioma (adjusted OR=6.05，95％CI=2.48-14.74for CC and adjusted OR=1.55，95％CI=1.11-2.16for CT),compared with the TT genotype. Compared to SOD216Val homozygotes, carrierswith the SOD216Ala allele exhibited more than a1.86-fold increased risk of gliomaoccurrence (adjusted OR=1.86;95%CI=1.35-2.55), with the risk increasingsignificantly with the increasing number of variant alleles (P-trend <0.001). Similarly,individuals with the SOD358A allele showed a significant association with the risk of glioma compared to the58T homozygotes (adjusted OR=1.64;95%CI=1.20–2.23; P-trend <0.001). We found no association between SNPs （the SOD2rs5746136and SOD3rs2695232）genotypes and glioma risk even after adjusting byconfounder factors in multifactor logistic analysis. PartⅡ Genetic Polymorphism in the GPX1are associatedwith Glioma susceptibility: A case-control analysisGPX1encodes the antioxidant glutathione peroxidase isoform1and acts inconjunction with the tripeptide glutathione (GSH), which is present in cells in high(micromolar) concentrations. Accumulating data link the alteration or abnormality ofGPX1expression to the etiology of cancer. The additional identification of GPX1polymorphisms, concordant with several other studies, suggests the involvement ofGPX1variants in the etiologies of glioma. To test the hypothesis that GPX1polymorphisms play a role in the etiology of glioma in Chinese populations, we alsoconducted a hospital-based case-control study in Jiangsu Province, in which weperformed genotyping analyses for GPX1polymorphisms.The results show that the GPX1gene rs1800668variant genotypes (CT+TT)were associated with a significantly increased glioma risk, compared with theirwild-type homozygote. CT variant genotypes individualized increased the risk ofglioma about5%, but did not reach significance level (adjusted OR=1.05,95%CI=0.72-1.53) compared to CC genotypes. Logistic regression analysis revealed that thers1800668TT variant genotypes associated increased risks for glioma compared withthe CC genotype homozygous (adjusted OR=3.30,95%CI=1.07-10.24). On theother hand, the dominant model shows that the individual risk for carrying the mutantgenotype (CT+TT) increased by18%(adjusted OR=1.18,95%CI=0.82-1.69). PartⅢ A Case-control Study on the Relationship betweenthe Genetic Polymorphism of NOS Gene and Susceptibilityto GliomaNitric oxide (NO), a pleiotropic messenger molecule, is mainly produced fromthe precursor L-arginine by neuronal nitric oxide synthase (NOS1) in the centralnervous system. In the current study, we tested the hypothesis that polymorphisms inNOS are associated with glioma susceptibility in a case-control study of400patientswith incident glioma and400frequency-matched cancer-free controls in Chinesepeople. Genotyping five common polymorphisms (minor allele frequency>0.10) inNOS using Taqman to determine the predisposition of individuals to glioma was thenperformed.In this population sample, the NOS1rs2682826may play a protective role in thedevelopment of glioma under the dominant model (adjusted OR=0.61;95%CI=0.45–0.82; P-trend=0.017). The variant genotypes of NOS1rs2682826homozygotesTT carriers confered a decreased cancer risk (adjusted OR=0.87,95﹪CI=0.47-1.59),compared with wild types. Some indication of significantly decreased glioma riskwith the NOS1rs2682826variant CT (adjusted OR=0.57;95%CI=0.42-0.79),compared with the CC genotype homozygous. |
PDF Full Text Request