Interaction between fragile histidine triad methylation, protein expression and human papillomavirus 16 infection in cervical carcinogenesis / 中华流行病学杂志

ABSTRACT

Objective To investigate the association between fragile histidine triad (FHIT) gene methylation,abnormal protein expression and HPV16 infection as well as their interactions in cervical carcinogenesis.Methods A total of 108 patients with normal cervical (NC),142 cases of cervical intraepithelial neoplasia (CIN1,n=72;CIN2 +,n=70),and 100 new cases of cervical squamous cell carcinoma (SCC) were chosen from the Shanxi Tumor Hospital,Second Hospital of Shanxi Medical University,Maternal and Child Health Center in Taiyuan and Jiexiu during September 2009 and March 2011.HPV16 was detected by multiple PCR.FHIT methylation and protein expression levels were detected by methylation specific PCR (MSP) and Western Blot,respectively.All the data were performed with SPSS 20.0 statistical softvare.Differences among groups were assessed by Chi-square and Kruskal-Wallis tests.The interaction effects were evaluated by additive model.Results The prevalence rates of HPV16 infection in CIN1 (45.8％),CIN2+ (68.6％) and SCC (73.0％) were significantly higher than that in NC (28.7％,P＜0.001).In NC,CIN1,CIN2+ and SCC groups,the FHIT gene methylation rates were 3.7％,13.9％,21.4％ and 38.0％ while the protein expression levels were 1.255 ± 0.130,1.184 ± 0.172,1.133 ± 0.126 and 1.099 ± 0.148,respectively.Differences among the groups were statistical significant (P＜0.001).With increasing degrees of cervical lesions,the HPV16 infection rate (x2=47.623,P＜0.001),FHIT methylation rate (x2=40.147,P＜0.001) and the rate of FHIT protein low expression (x2=65.098,P＜0.001) were all gradually increasing.There appeared positive additive interaction between FHIT methylation,FHIT protein low expression and infection of HPV16.Conclusion Hypermethylation of FHIT gene,low expression of FHIT protein and HPVI6 infection could increase the risk of cervical cancer and precancerous lesions.These results suggested that there might be synergistic action between FHIT gene hypermethylation and HPV16 infection in the progression of cervical cancer and the same was true between the low expression of FHIT protein and HPV 16 infection.