结核杆菌感染与原发性肺癌FHIT基因缺失的关系研究

The nested polymerase chain reaction (N-PCR) technique , in site polymerase chain reaction(IS-PCR),PCR-SSCP and LOH was used to detect mycobacterium tuberculosis (TB) and the fragile histidine triad (FHIT) gene alteration in 63 primary lung cancer patients and 10 pulmonaty tuberculosis patients. The lung cancer patients with PPT were detected TB-DNA in 7 of 10 , significantly higher than that of lung cancer patients without PPT [Fisher's Exact Test, P=0.034 (2-sided)]. TB-DNA were found mainly in plasma of alveoli epithelial cells and alveolar macrophages within lung cancer tissues. The lung cancer patients(11/12) with positive TB was significantly higher than that(12/24) with negative TB in the frequency of losses of FHIT gene( Fisher's exact test p = 0.025, logistic regression analysis,p= 0.042). Loss of heterozygosity (LOH ) affecting at least two locus of the FHIT gene was observed in 6 of 10 tumors in the PPT group (60%) but in only 3 of 26 tumors without PPT (11.5%), the frequency of losses at least two locus of the FHIT gene,was significantly different (Fisher's exact test p = 0.006, logistic regression analysis p= 0.024). Atypical hyperplasia around chronic pulmonary tuberculosis formations showed the losses of FHIT gene. These results suggest that TB chronic infection could play a role in the pathogenesis of lung cancer related with PPT, FHIT is probably a candidate molecular target of carcinogens contained in PPT.

本研究采用荧光定量PCR、原位PCR观察结核杆菌DNA在原发性肺癌、肺结核患者血和组织中姆植迹⒂τ靡痉峭凰豍CR-SSCP技术检测组织中FHIT基因缺失情况，以期从分子水平教纸岷烁司腥居敕伟┓⑸墓叵导盎疲伟?一级预防和早期诊断提供可靠的理论依据，为肺癌基因治疗、免疫治疗开辟新的途径。