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Etiopathogenesis of broncogenic carcinoma
- 1. CORRELATION SEMINAR ON BRONCHOGENIC CARCINOMA RESPIRATORY SYSTEM PUSPA RAJ BHAM(ROCHAKGYANSAGAR) ROLLNO.1880 MAHARAJGUNJMEDICALCAMPUS,IOM. 4/9/2020 1
- 2. OBJECTIVES • To describe etiopathogenesis of bronchogenic carcinoma 4/9/2020 2
- 3. Bronchogenic Carcinoma • Cancer of lungs tissues, epithelial origin • Most common cause of cancer mortality • Most frequently diagnosed • Occurs in between 40-70 yrs • Peak incidence ; 50s and 60s 4/9/2020 3
- 4. Etiopathogenesis • Tobacco smoking ( most common ) • Industrial hazards • Air pollution • Dietary factors • Molecular genetics 4/9/2020 4
- 5. Tobacco Smoking • 80% of lungs tumor in active smokers and those stopped recently • 60 times greater risk among habitual smokers • • There is linear correlation between lung cancer and pack years of smoking • Women have higher susceptibility to carcinogens in tobacco than male • Mutagenic effects of carcinogens are modified by genetic variation 4/9/2020 5
- 6. Tobacco Smoking • Highly pleomorphic P-450 monooxygenase enzyme • Individual whose peripheral blood lymphocytes show more numerous chromosomal breakages after exposure to carcinogens of cigarette have 10 fold higher risk • Carcinogens of tobacco: tar , polycyclic aromatic hydrocarbon, nitrosamines • Cigar and pipe smoking • Passive smokers have double risk than non smokers 4/9/2020 6
- 7. Industrial hazards • Asbestos , arsenic , chromium , uranium , mustard gas • High dose ionizing radiation • Uranium , 4 times risk among non smokers , 10 times risk among smokers • Asbestos , 5 times risk among non smokers , 55 times risk among smokers 4/9/2020 7
- 8. Air pollution • Add to the risks in smokers and second hand smokers -Radon gas 4/9/2020 8 Chronic exposure to air particulate Lung irritation Inflammation repair
- 9. Dietary factors Susceptibility of bronchogenic carcinoma is increased in conditions of vitamin A deficiency 4/9/2020 9
- 10. Molecular genetics Stepwise accumulation of oncogenic driver mutations Neoplastic transformation of pulmonary epithelial cells 4/9/2020 10
- 11. Squamous cell carcinoma • Chromosome deletion involving tumor suppressor loci 3p,9p ,17p • Loss of expression of RB tumor suppressor gene 4/9/2020 11
- 12. Small cell carcinoma • Loss of function mutation of TP53(75%-90%) , RB(close to 100%) , chrosmosomal 3p deletions • Amplification of genes of MYC family 4/9/2020 12
- 13. Adenocarcinoma • Gain of function mutation of proto-oncogenes • Mutation of gene encoding receptor tyrosine kinase: EGFR, ALK, ROS, MET, RET • Tumors without mutation in tyrosine kinase have mutation in KRAS 4/9/2020 13
- 14. Lung cancer in never smokers -25%of lung cancer occur in never smokers -Mostly in women and adenocarcinoma -Likely to have EFGR mutation 4/9/2020 14
- 15. Pre-invasive lesion Begins with basal cell hyperplasia Squamous metaplasia Squamous dysplasia Carcinoma in-situ Invasive cancer 4/9/2020 15
- 16. 4/9/2020 16
- 17. Bibliography • Robbins and Cotran Pathologic Basis of Disease , 10 th edition • Textbook of Pathology , 6th edition : Harsh Mohan 4/9/2020 17
- 18. Thank you ! 4/9/2020 18