| Background and objective: Increasing incidence and mortality of tumoris the most important cause of death in worldwide. Risk factors for thedevelopment of cancer are smoking, drinking, environment, geneticfactors and so on. Single nucleotide polymorphism (SNP) is the mostcommon genetic variation in the human genome. In recent years, SNPnamed as the third genetic marker for human, is a critical factor for thedisease susceptibility, drug susceptibility, and the response of environmentfactors. SNP in microRNA or microRNA-binding sites can influence therisk of certain human diseases by either binding microRNA to messengerRNA (mRNA) or regulating the expression of its target genes. ThemiR-502binding site SNP in the3’-UTR of set domain-containing protein8(SET8) rs16917496and tumor protein p53(TP53) gene exon4(codon72) polymorphism are both related to the formation and development ofcancer. The express product of SET8methylates TP53and affects genomestability. This study was to examine whether polymorphic variants ofSET8and TP53codon72were associated with increased risk for tumor(lung cancer or cervical cancer), either independently or jointly, andinvestigate the correlation between the polymorphic variants andparameters of clinical pathology.Methods: Peripheral blood samples from164lung cancer patients and199controls,114cervical cancer patients and200controls were collectedfrom January2011to December2013in Hunan, China. The basic data andparameters of clinical pathology were recorded. The genotypes of SET8gene and TP53codon72were confirmed by polymerase chainreaction-restriction fragment length polymorphism (PCR-RFLP) anddirect DNA sequencing. Statistical Package for the Social Science (SPSS)13.0was used to analyse the association between the gene polymorphicvariants of SET8gene and TP53codon72and cancer risk, and thecorrelation between polymorphic variants and parameters of clinicalpathology.Results: There was a significant difference between lung cancer casesand controls in smoking, smokers were more common in patients than incontrols (65.2%vs.39.2%; P<0.05). It is indicated that smoking was a high risk factor for lung cancer in this study (OR=2.912;95%CI=1.896-4.473). Compared with the CC genotype, SET8TT genotype wasassociated with an increased risk for the incidence of lung cancer (OR=2.173;95%CI=1.045-4.517). Compared with the CC genotype, the TP53GG genotype was associated with an increased risk for the development oflung cancer (OR=2.579;95%CI=1.366-4.870). In additional, interactionbetween the SET8and TP53polymorphisms increased the risk of lungcancer (OR=3.032;95%CI=1.580-5.816), with the frequency of theSET8CC and TP53GG genotypes was significantly higher. There was nocorrelation between the genotypes of SET8gene and TP53codon72andthe parameters of clinical pathology in lung cancer.There was a significant difference between cervical cancer cases andcontrols in smoking, smokers were more common in patients than incontrols (17.5%vs.6.5%; P<0.05). It is indicated that smoking was ahigh risk factor for cervical cancer in this study (OR=3.061;95%CI=1.459-6.421). Compared with the TT genotype, SET8CC genotype wasassociated with an increased risk for the incidence of cervical cancer(OR=2.717;95%CI=1.436-5.141). Compared with the CC genotype,the TP53GG genotype was associated with an increased risk for thedevelopment of cervical cancer (OR=2.168;95%CI=1.149-4.089). Inadditional, interaction between the SET8and TP53polymorphismsincreased the risk of cervical cancer (OR=9.913;95%CI=2.028-48.459),with the frequency of the SET8CC and TP53GG genotypes wassignificantly higher. There was no correlation between the genotypes ofSET8gene and TP53codon72and the parameters of clinical pathology incervical cancer.Conclusion: In summary, our study showed a significant associationbetween the polymorphism (rs16917496) of the miR-502-binding site inthe3’-UTR of SET8or/and TP53codon72polymorphism and the risk ofdeveloping lung cancer and cervical cancer, either independently orjointly. |
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