Relationship Among HPV Infection, FHIT Deletion And Lung Cancer In Nonsmoking Female

IntroductionLung cancer is a serious problem in public health;the morbidity and the mortality have been increasing rapidly.It is shown that most of the cases are non-smoking women,and the risk factors are still unclear.An association of human papillomavirus (HPV)infection with lung cancer among non-smoking women was revealed in previous study.The fragile histidine triad(FHIT)gene had been reported a frequent deletion in smoking lung cancer and HPV-associated cervical cancer.In our study,we investigate aberrant transcripts of FHIT gene in non-smoking female lung cancer, explore its relation with HPV infection and assess the gene-environmental interaction.Materials and MethodsThere were 60 patients with histologically confirmed incident lung cancer recruited before any radiotherapy or chemotherapy.Control women without a previous diagnosis of cancer were recruited from the same hospital,with age as matching criteria. All of lung cancer specimens and benign lesion specimens were examined for the fragment of HPV-DNA by PCR,using RT-PCR to detect aberrant transcripts of FHIT. Questionnaire,including the character of demography,the history of passive smoking, the exposed history of cooking fume,the fuel exposure,the exposed history of coal fume,the history of previous diseases of lung,the cancer history of relatives and the occupational history,was used to detect risk factors of non-smoking female lung cancer. All of the statistical analyses were performed by the SPSS statistical,software(version 13.0).Pearson′s x~2 test and Fisher exact probability test were used to test the differences between the case and control.ORs and 95%CIs were calculated as an estimate of the relative risk.Use crossover analysis to assess the gene-environmental interaction.RERI,S,AP were calculated for the interaction.ResultsThe prevalence for HPV L1,HPV 16 and HPV18 is 31.67%(19/60),20.00% (12/60)and 18.33%(11/60),respectively.HPV 16 had a higher prevalence in cancer tissue than that in benign lesion tissues(P=0.032),OR is 3.500.FHIT aberrant transcripts is more frequently in female with lung cancer than that in female with benign lesion,OR is 4.016(95%CI:1.831～8.806).It was also associated with HPV 16 infection in cancer tissues(OR is 5.435,P＜0.05).Calculated by crossover analysis based on additive model,relative excess risk of interaction(RERI),attributable proportion of interaction(AP)and synergy index S(S)appeared to be 5.667,64.4%, 3.657(P＜0.05),respectively,for gene-environment interaction between HPV infection and FHIT aberrant transcription.Conclusions1,HPV,especially high risk HPV infection contributes to lung cancer in non-smoking female.2,There are more FHIT aberrant transcripts in HPV infection patients,especially in HPV 16 infection female.3,In lung cancer among women nonsmokers,HPV infection and FHIT aberrant transcripts have sum model interaction.