Association Of Polymorphism In DNMT3B Gene With Susceptibility Of Non-Small-Cell Lung Cancer In Chinese Population

Lung cancer is the leading cause of cancer-related death for both men and women in the world. The occurring of tumor is due to general effect of individual heritability and environmental factors. A global epigenetic alteration such as DNA methylation has been reported to play a significant role in the development and progression of various cancers. The methylation status for cancer cells is typically globally hypomethylated and also gene-specific hypermethylated, this being especially the case for tumor-suppressor genes. In such cases, DNA methylation is typically mediated by DNA methyltransferases (DNMTs), specifically DNMT1,DNMT3A and DNMT3B. Although DNMTs act cooperatively in order to achieve the establishment and maintenance of a genomic methylation pattern, DNMT1 is considered as a maintenance DNA methyltransferase due to its ability to preferentially methylate hemimethylated DNA subsequent to DNA replication. DNMT3A and DNMT3B function as de novo methyltransferases, which reportedly methylate unmethylated and hemimethylated DNA.Among these DNMTs, DNMT3B plays a crucial role in tumorigenesis that is significantly over-expressed for several different tumor types. Recently, a single nucleotide polymorphism (SNP) of the DNMT3B promoter (C46359T) was reported to be crucial for its promoter activity resulting in an involved individual's predisposition to certain cancers.Objective: To investigate the association between single nucleotide polymorphism(SNP) of DNA methyltransferase 3B promoter(C46359T) gene with susceptibility to the severity of non-small cell lung cancer.Methods: This study was divided into two groups. 52 patients with histologically confirmed non-small cell lung carcinoma who ever underwent surgery treatment at the Department of Thoracic surgery, No2 Hospital, Jilin University between 2006 and 2007 were selected as case group. The control group that include 55 members was selected from cancer-free individuals who conduct medical check-up in No2 Hospital, Jilin University. All subjects were phlebotomized 5ml of blood and leucocyte DNA was extracted by DNA extraction kit. The DNMT3B gene SNPs were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Statistical analysis was performed using SPSS 13 software package. Using Chi-square test performed comparison of the DNMT3B genotype and allelotype distribution in the study groups. Probability values less than 0.05 were considered to indicate statistical significance.Results: (1) The distribution of the DNMT3B genotypes in both NSCLC patients and healthy controls were accorded with Hardy-Weinberg equilibrium(all P values are above 0.05) .(2) The C/C genotype was not detected in both controls and NSCLC patients.The allelic frequencies of C and T were 2.7% and 97.3% in controls respectively, and 4.8% and 95.2% in cases. There was no difference of allele frequencies in two groups(P>0.05).(3)The genotype distribution of C/C, C/T and T/T were 0, 9.6% and 90.4% in the lung cancer group, 0, 5.7% and 94.3% in the healthy control group respectively, There was no difference between the two groups(P>0.05).(4)No remarkable association was observed between the genotype distribution of DNMT3B and the pathological type in the patient with lung cancer. Conclusion:(1) DNMT3B gene polymorphism may not be associated with the susceptibility in NSCLC patients of North China.It may not be used as marker to predict susceptibility in the population of North China. (2) No remarkable association was observed between the genotype distribution of DNMT3B and the pathological type in the NSCLC patient.(3) Based on literature analysis,there are significant differences in DNMT3B genotype distributions between China northerners and Caucasian.