Association Study Of Single Nucleotide Polymorphisms In Chromosome 6q22.2 Locus With Lung Cancer Susceptibility

Purpose In our country, lung cancer is one of the common malignant tumors, whose incidence and mortality are in the first of all tumors. The occurrence of lung cancer is a complex process. Due to Genome-wide association study(GWAS) analysis the variation of the entire genome, it was proved to be an effective method to the study of complex diseases. In recent years, GWAS studies have identified multiple polymorphic locus associated with susceptibility to lung cancer, but the biological functions of this locus are still unknown. Post-GWAS study is critical to discover the molecular mechanism. In this study, we analyzed the biology function of the previous GWAS identified SNP rs9387478 associated with lung cancer risk.Methods We preformed linkage disequilibrium analysis to previous GWAS identified lung cancer susceptibility loci rs9387478. We select four potential function SNPs(rs17079281 rs6911915 rs9320604, rs4946259) to further analysis. We select 766 cases confirmed by pathological histology diagnosis from Tianjin Medical University Cancer Institute and Hospital; Control group were from the same period health check-up crowd, according to frequency of sex and age matched group cases. We get clinical pathological data by looking at the patient medical records. Follow-up information was got by phone or checking the outpatient records. Clinical data was obtained through the questionnaire survey in the control group. Taqman probe genotyping technique was used to genotyping case group and the control group.Unconditioned logistic regression analysis the relationship between gene polymorphism and susceptibility to lung cancer in codominant model, the dominant model and recessive model. Biology information was used to predict potential function of SNP associated with lung cancer susceptibility. Luciferase report gene experiment detected the effect of gene polymorphisms on its target gene transcription activity. Real-time fluorescence quantitative polymerase chain reaction detects the DCBLD1 m RNA expression of lung cancer tissues. We further analyze its relationship between gene polymorphism and clinical pathological features of patients.Wound-healing and Transwell migration and invasion analysis the effect of DCBLD1 and YY1 on lung cancer cell migration and invasion ability.Results In addition to the rs9320604 rs4946259, rs17079281, rs6911915 met Hardy Weinberg equilibrium(P > 0.05). In the codominant model case-control study found rs17079281, rs6911915 associated with the risk of lung cancer; Compared with carry rs17079281 CC genotype, CT genotype carriers have a lower incidence of dangerous(OR = 0.74; 95% CI: 0.58 0.94); Compared with TT genotype, rs6911915 CT genotype has lower the risk of lung cancer(OR = 0.77; 95% CI: 0.59 0.99); Other rs9320604, rs4946259 has nothing to do with lung cancer risk. In the dominant model analysis found that compared with the rs17079281 CC genotype, T genotype carriers have a lower risk of lung cancer(OR = 0.78; 95% CI: 0.63 0.98); other genotype has nothing to do with lung cancer risk. We found no significant statistics relationship between SNPs and prognosis of lung cancer.Biology information found that rs17079281 affect the combination of transcription factor YY1 with DCBLD1 promoter region. Luciferase results show that the combination of the transcription factor YY1 and rs17079281 T allele inhibit transcription activity. Compared with CC genotype, DCBLD1 m RNA expression in lung cancer tissue with T allele has a tendency to downregulation. However there was no statistically significant difference(P > 0.05). There were significant differences in the expression levels of DCBLD1 and YY1m RNA between gender, smoking status,histology subtype, clinical stages(P < 0.05). In vitro experiment showed that the DCBLD1 promoter lung cancer cells migration and invasion and YY1 inhibit lung cancer cells proliferation, migration and invasion.ConclusionSNP rs17079281 may affect the binding affinity of YY1 to DCBLD1 and influence the risk of lung cancer. Ectopic expression of DCBLD1 and YY1 affect tumor biologic behavior of lung cancer cell A549 and H1299.