Tuberculosis and Lung Cancer: Features of Carcinogenesis

Abstract

Epidemiological data have shown an association between tuberculosis and an increased risk for the development of lung cancer. It is believed that the rate of development of bronchogenic carcinoma is higher in patients with pulmonary tuberculosis than in the individuals without respiratory disease. The incidence of co-existent lung cancer and tuberculosis is accounted from 1% to 16%. Several factors are involved in neoplastic transformation, one of which is infectious agents, though correlation between tuberculosis-related chronic inflammation and the development of lung cancer is not fully understood. The intense inflammatory response to mycobacteria, which is characterized by the release of inflammatory mediators such as tumor necrosis factor, interferon-gamma and interleukins, that occurred in granulomas during the active tuberculosis can cause damage to the lung tissue. Matrix metalloproteinases, which can promote lung remodeling in tuberculosis, are also involved in the process of damage to the extracellular matrix of the lung tissue. In addition, the regeneration process contributes to the development of fibrosis, which is also a factor for the development of lung cancer. The role that scars can play in the pathogenesis of the tumor process is unclear. However, neoangiogenesis, which is a necessary part of tissue regeneration, is crucial for tumor growth. Several studies show that post-tuberculosis lung cancer is not of bronchial origin, but rather arises from the scar tissue. Moreover, enhanced cell proliferation during the recovery process in chronic inflammation can lead to metaplasia and subsequent changes, such as dysplasia, which are regarded as precancerous conditions. Recent studies have shown that the mpb64 gene, characteristic of Mbt-L, has been detected in the tuberculosis tissue specimens, lung cancer tissue specimens, and co-existence of both. Cytogenetic analysis of lung cancer and dysplastic lesions of the bronchi showed that in these pathologies a deletion of the short arm on chromosome 3 is often noted, the critical gene on which is FHIT. The latter encodes a small mRNA and a small protein of the same name, involved in the processes of apoptosis and regulation of transcription. According to some reports, lung cancer may arise from the claviform cells as a result of mutations under the influence of various exogenous and endogenous factors, including chronic inflammation. Recent studies have found that scar carcinoma was represented by adenocarcinoma and squamous cell carcinoma of varying degrees of differentiation. The tumor nodule in tuberculoma was associated with its fibrous capsule and represented by the same histological variants. However, in fibrocavernous tuberculosis, the formation of squamous cell carcinoma was noted, and, notably, in most cases, its occurrence was associated with active inflammatory process in the cavity wall. Conclusion. It can be stated that chronic inflammation, pneumosclerosis, disrupted immunological control and intercellular regulatory interactions contribute to the accumulation of genetic rearrangements and mutations leading to malignant transformation