The Association Between The Infection Of Mycobacterium Tuberculosis And The FHIT Gene Deletion Of Lung Cancers With Pevious Pulmonary Tuberculosis

Recently It has been focused on the relationship between germ infection and cancer. Epidemiological evidence suggests that previous pulmonary tuberculosis (PPT) is an independent risk factor for lung cancer, which can't be explained by active or passive smoking alone. Although a number of mechanisms have been proposed to explain the possible association, the precise mechanism by which the PPT may enhance carcinogenesis is still unclear. FHIT (fragile histidine triad) gene as a tumor suppressor gene, usually plays an important role in the progression from normal to premalignant lesion in the lung and is a target of environmental carcinogens. In order to evaluate the association between mycobacterium tuberculosis(M-TB) infection and PPT related lung cancer, and identify the characteristic of genetic lesions of PPT damage, the nested polymerase chain reaction (N-PCR), in site polymerase chain reaction(IS-PCR), PCR-SSCP, loss of heterozygosity (LOH), tissue array and immunohistochemical method were used to detect M-TB and the FHIT gene alteration in 61 primary lung cancer patients and 20 pulmonary tuberculosis patients. The results showed that: (1) M-TB was detected in 22 of 61 lung cancer tissues (36.1%). The M-TB positive rate of lung cancer patients with PPT(70%,7/10) was significantly higher than that of lung cancer patients without PPT(29.4%, 15/51) [Fisher's Exact Test, P=0.027 (2-sided)]. (2) M-TB was detected mainly in plasma of lung epithelial cells and alveolar macrophages around cancer tissues, and in interstitium of cancer tissues. (3)Absence of FHIT gene transcript was mainly in exon 3~6, LOH affecting at least one microsatellite locus of the FHIT gene was observed in 23 of 36 lung cancer (63.9%), 68.8%(22/32) lung cancer showed absent or reduced FHIT protein expression. (4) The lung cancer patients (11/12) with positive M-TB was significantly higher than that (12/24) with negative M-TB in the frequency of losses of FHIT gene (Fisher's exact test P = 0.025, logistic regression analysis, P=0.042). (5) LOH affecting at least two microsatellite loci of the FHIT gene was significantly different between tumors with PPT (6/10, 60%) and tumors without PPT (3/26, 11.5%), Fisher's exact test P=0.006, logistic regression analysis P=0.024. (6) Atypical hyperplasia around chronic pulmonary tuberculosis focus, partly showed the loss of FHIT gene and absent or reduced protein expression. (7) Point mutations within the coding region (exon 5, exon 8) of the FHIT gene were not detected in all lung cancers.We first concluded that M-TB chronic infection could play an important role in the pathogenesis of lung cancer related with PPT, FHIT is probably a candidate molecular target of carcinogens contained in PPT.