Objective To investigate the expression of FHIT,WWOX and MDR1 gene in nasopharyngeal carcinoma and FHIT and WWOX mechanism of inactivation.Methods Real-time PCR was used to test FHIT,WWOX and MDR1 gene′s mRNA expression in 89 nasopharyngeal carcinoma patients (experimental group) and 61 inflammatory patients (control group).Q-MSP was used to test the FHIT and WWOX promoter methylation status.Denatured polyacrylamide gel electrophoresis was used to test the LOH of FHIT and WWOX gene.Results (1)The three genes′ mRNA expression were different between experimental group and control group (P<0.05).After grouped according to the histological type and clinical stages,the expression of FHIT and WWOX mRNA between the patients with serious illness or poorly differentiated squamous cell carcinoma and mild cases or highly differentiated squamous cell carcinoma were significantly different in the experimental group,the difference is statistically significant (P<0.05)Meanwhile,the FHIT and WWOX mRNA expression had statistical association with the clinical stage and histological type(r=-0.731,P=0.000;r=-0.816,P=0.000;r=-0.626,P=0.000;r=-0.536,P=0.001).The MDR1 mRNA expression was different between poorly and highly differentiated squamous cell carcinoma (P=0.021),which was statistical associated with the histological type (r=-0.697,P<0.001).(2)The degrees of FHIT and WWOX promoter methylation in the experimental group was higher than those in the control group,the difference was statistically significant (P<0.05);Also,the expression of FHIT and WWOX mRNA were closely related to the degree of promoter methylation(r=-0.689,P=0.000;r=-0.594,P=0.000).(3) In the experimental group,there were 39 cases (43.8%) of LOH in the FHIT gene,and 42 cases (47.2%)of the WWOX genes were significantly higher than those in the control group (4.9% and 3.3%),the difference was statistically significant (P<0.05).The FHIT and WWOX gene mRNA were negatively correlated with the loss of heterozygosity(r=-0.239,P=0.049;r=-0.364,P=0.013).Conclusion Promoter methylation is the main reason for the down-regulation of FHIT gene and WWOX gene expression in nasopharyngeal carcinoma patients,which may be the main reason for the occurrence and development of nasopharyngeal carcinoma.The higher expression of MDR 1 mRNA is statistical association with the histological type.