ABSTRACT
Objective To explore the relationship between MTHFR gene polymorphism and lung cancer in Han population of Heilongjiang Province.Methods Two hundred and twenty-five lung cancer patients were selected as the experimental group and the healthy subjects in the outpatient physical examination as the control group,A case-control study was used to analyze the association of MTHFR gene 677C/T,1298A/C SNP and lung cancer,and the gene typing was detected by Sanger double deoxidization chain termination method.Results In the control group,the frequencies of wild-type CC,mutant heterozygote CT,and homozygous TT genotypes of the MTHFR gene C677T were 34.2％,55.1％,and 10.7％,respectively.The frequencies of the three genotypes in the experimental group were 26.7％,50.2％,23.1％,respectively.The difference in the distribution of C677T SNP genotype frequencies of the experimental group and the control group was statistically significant (P =0.002),in which the mutation homozygous TT carriers were 2.78 times more likely to develop lung cancer than wild-type CC (OR(95％CI):2.78 (1.54 ～ 5.02),P =0.001);AA,AC and CC genotype frequencies ofthe A1298C locus of the MTHFR gene were 34.2％,55.1％,and 10.7％,respectively,and the control group was 64.0％.32.0％,4.0％,there was no significant difference between the two groups (P =0.247).The frequencies of AA,AC and CC genotypes in the A1298C locus of the MTHFR gene were 34.2％,55.1％,and 10.7％,respectively,and 64.0.％,32.0％,and 4.0％ in the control group,respectively.There was no significant difference between the two groups (P).=0.247).The haploid analysis showed that the distribution frequency of TA haplotype in the experimental group was significantly higher than that in the control group (43.1％ vs.35.3％).There was a statistically significant difference between the two groups (OR(95％CI):1.39 (1.06-1.81),P=0.016);while the frequencies of CC haplotypes in the experimental group and the control group were 10.6％ and 17.1％,respectively.The difference was statistically significant (OR(95％CI):0.58 (0.39-0.85).P=0.005).There was a linkage disequilibrium between the two points of MTHFR gene 677 and 1298 (D'=0.48,P=0.003).The gene-environment interaction analysis of the MTHFR gene C677T polymorphism showed that based on the comparison between TT and CC genotype,age over 60 (OR(95％CI):4.0(1.78-9.32),P =0.001),male (OR (95％CI):5.55 (2.10-14.67),P=0.000),smoking (OR(95％CI):8.13 (2.29-28.85),P=0.000) and small cell lung cancer (OR (95％CI):1.28 (1.10-1.44),P=0.000) can increase the risk of lung cancer;based on the comparison between CT and CC genotype,women (OR(95％CI):2.09 (1.05-4.16),P=0.030),non-smoking population (OR(95％CI):2.43 (1.25-4.74),P=0.008) and small cell lung cancer (OR (95％ CI):0.31 (1.16-1.59),P =0.000) can increase the risk of lung cancer.Conclusion MTHFR gene C677T is a genetic susceptibility gene for lung cancer and is associated with the risk of lung cancer.