The relationship between previous pulmonary tuberculosis and risk of lung cancer in the future

Abstract

Various investigations have expanded the views that tuberculosis is an important risk factor for lung cancer occurrence. Lung cancer originates from chronic inflammation and infection. It is becoming clearer that Mycobacterium tuberculosis (M.tb) in tuberculosis patients meticulously schemes multiple mechanisms to induce tumor formation and is indispensable to participate in the occurrence of lung cancer. In addition, some additional factors such as age, sex and smoking, accelerate the development of lung cancer after Mycobacterium tuberculosis infection. The clarification of these insights is fostering new diagnoses and therapeutic approaches to prevention of the patients developing from tuberculosis into lung cancer.

Keywords: COX-2; CRP; Cytokine; DNA damage; Lung cancer; ROS; Risk factor; Tuberculosis.

Fig. 1

M.tb promotes proliferation and migration of A549 cells. BCG induces SHH signaling-dependent expression of COP1, which targets and degrades of P53, and it inhibits cell apoptosis of A549. PtpA-expressing BCG can promote proliferation and migration of A549 cells, partially through targeting GADD45A or ncRNA genes (such as miR-488, CASC2, and miR-622) which are related to tumor progression through regulating cell apoptosis, proliferation, and migration. NOX4-p62 might serve as a driving factor of the tumor microenvironment changed by tuberculosis fibrosis. Mce2E of M.tb can inhibit eEF1A1, which increase cell proliferation. These actions all promote proliferation and migration of A549

Fig. 2

M.tb plays an important role in carcinogenesis in the lungs resulting from generation of reactive oxygen species (ROS) in the macrophage and alveolar epithelial cell. ROS can damage DNA and induce DNA mutation, that initiate tissue remodeling and pulmonary fibrosis, which promotes lung cancer. ROS also upregulate oncogenes jun and fos, which are involved in cell cycle progression through inhibition of P21, that promote cell division and inhibit apoptosis. In mitochondria, mtROS damages mtDNA and induce AEC apoptosis through interrupting respiratory chain and mitochondrial function, which leads to pulmonary fibrosis and lung cancer

Fig. 3

The role of COX-2 in tumorigenesis. COX-2 is induced in the DC cells and monocytes infected with M.tb. On the one hand, promotion of tumor metastasis of COX-2 depends on the p-Akt-NF-κB pathway affecting the activity of MMP-9. On the other hand, up-regulation of COX-2 can increase BCL-2 synthesis to inhibit apoptosis, and BCL-2 inhibits mitochondrial-mediated apoptosis pathway, mitochondrial dysfunction aggravates DNA damage, which further promotes cell mitosis and tumorigenesis

Fig. 4

The relationship between tuberculosis and lung cancer

Fig. 5

The incidence of tuberculosis and lung cancer in indicated countries