Study On The Relationship Between Methylation Of Folic Acid Metabolism And Other Related Genes With Kazakh Esophageal Cancer And Prognosis

Objective: To investigate the relationship between the hypermethylation status of MTHFR,CBS and MGMT,P16,FHIT,RASSF1 A and Kazakh esophageal cancer,and to analyze the prognostic factors of Kazak esophageal cancer.The aim of this study was to provide basis for the prevention and control of Kazak esophageal cancer Cancer.Methods: 192 patients of esophageal cancer and 200 patients of non-esophageal cancer in Xinjiang were collected from 2010 to 2015.Ion Capture Immunoassay(ICIA)were used to measure serum folic acid levels,methylation-specific polymerase chain reaction(MSP)technique was used to detect the expression of MTHFR,CBS,MGMT,P16,FHIT and RASSF1 A gene promoter methylation level,Log-rank test and Cox model were used to analyse the factors affecting the prognosis of Kazakh esophageal cancer.Results: 1.The levels of serum folic acid in the case group were lower than control group(Z=—9.13,P=0.000),the difference was statistically significant;2.Analysis of gene methylation level:The methylation rate of MTHFR,CBS,MGMT,P16,FHIT and RASSF1 A gene in the case group were higher than that in the control group,the difference were statistically significant(?~2=45.144,P=0.000;?~2=18.465,P=0.000;?~2=11.853,P=0.003;?~2=37.359,P=0.000;?~2=46.608,P=0.000;?~2=14.766,P=0.001).3.The relationship between gene methylation and clinicopathological features: The methylation of MTHFR gene was associated with the sex,age and pathological types(?~2=4.099,P=0.043;?~2=12.800,P=0.005;?~2=9.851,P=0.020),the methylation of CBS gene was associated with the pathological types,infiltration degrees and TNM stages(?~2=24.463,P=0.000;?~2=4.488,P=0.034;?~2=6.412,P=0.041),the methylation of MGMT gene was associated with the tumor size,differentiation,regional lymph node metastasis and TNM stages(?~2=5.424,P=0.020;?~2=7.412,P=0.006;?~2=6.692,P=0.010;?~2=10.739,P=0.005),the methylation of P16 gene w a s a s s o c i a t e d w i t h t h e d i f f e r e n t i a t i o n,i n f i l t r a t i o n d e g r e e s a n d T N M stages(?~2=6.356,P=0.012;?~2=10.478,P=0.001;?~2=11.646,P=0.003),the methylation of F H I T g e n e w a s a s s o c i a t e d w i t h t h e p a t h o l o g i c a l t y p e s a n d T N M stages(?~2=15.479,P=0.001;?~2=12.564,P=0.002),the methylation of RASSF1 A gene was associated with the differentiation,regional lymph node metastasis and TNM stages(?~2=4.123,P=0.042;?~2=14.884,P=0.000;?~2=6.709,P=0.035),the differences were statisticallysignificant.4.Multivariate Cox regression analysis showed:Tumor infiltration degrees(?~2=7.961,P=0.005),regional lymph node metastasis(?~2=16.135,P=0.000),TNM stages(?~2=4.789,P=0.029;?~2=7.509,P=0.006),CBS gene methylation(?~2=6.212,P=0.013)and RASSF1 A gene methylation(?~2=6.355,P=0.012)were independent risk factors for the prognosis of esophageal cancer,female(?~2=4.981,P=0.026)and serum folic acid(?~2=8.794,P=0.003;?~2=8.165,P=0.004;?~2=5.130,P=0.024)were protective factors for the prognosis of esophageal cancer.Conclusions: The methylation of MTHFR,CBS,MGMT,P16,FHIT and RASSF1 A genes is closely related to the occurrence of esophageal cancer in Kazak in Xinjiang.Tumor infiltration degrees,regional lymph node metastasis,TNM stages,CBS gene and RASSF1 A gene methylation were independent risk factors for the prognosis of esophageal cancer.Female sex and serum folic acid are protective factors.