BMS100_PAT1.04_W23_Pre-learning 2_TO.pptx

Pathology Concepts 1.04 Carcinogenesis – Epidemiology & Risk Factors Dr. Hurnik BMS 100 Week 9 Video Link https://ccnm.ca.panopto.com/Panopto/ Pages/Viewer.aspx?id=ac2b76a3-ff224a0e-ab8a-afbb000bb842 Today’s Overview Pre-learning: Definitions & tumour characteristics Epidemiology & Risk factors...

Pathology Concepts 1.04 Carcinogenesis – Epidemiology & Risk Factors Dr. Hurnik BMS 100 Week 9 Video Link https://ccnm.ca.panopto.com/Panopto/ Pages/Viewer.aspx?id=ac2b76a3-ff224a0e-ab8a-afbb000bb842 Today’s Overview Pre-learning: Definitions & tumour characteristics Epidemiology & Risk factors In class: Model of carcinogenesis Tumor progression Oncogenes Ras, Myc, Cdks & cyclins Tumour suppressor genes RB, p53, CKIs, APC APC/Beta-catenin review Hallmarks of cancer Warburg effect Limitless replicative potential Carcinogens Assignment - HPV Cancer epidemiology • Notes Pathologic Basis of Disease(Robbins and Cotran) 10th ed. Figure 7 Risk factors • There are both genetic and environmental factors that can contribute to cancer risk  Best establish environmental risk factors include: Infectious agents Smoking Alcohol (oropharynx, upper GI cancers) Diet (colorectal, breast cancers) Obesity Reproductive history (cumulative exposure to estrogen without progesterone) • Environmental carcinogens • • • • • • Risk factors - age • Cancer can occur at any age, but most carcinomas occur in adults older than age 55  Likely explained by accumulations of somatic mutations that accompanies aging of cells  A decline in immune competence may also play a role Risk factors – Acquired conditions • Some acquired conditions increase the risk of cancer:  Chronic inflammatory disorders  Precursor lesions  Immunodeficiency states Risk factors – Chronic inflammation • Cancer risk is increase in individuals with a wide variety of chronic inflammatory diseases  Why? Many possible reasons, here are some examples: • Chronic inflammatory diseases is accompanied by tissue damage  Cell proliferation must occur to repair the damage • Activated immune cells produce reactive oxygen species that can damage DNA and therefore acquiring mutations that lead to carcinogenesis • Inflammatory mediators produced can promote cell survival (which prevents apoptosis) Risk factors – Chronic inflammation - examples • FYI Pathologic Basis of Disease(Robbins and Cotran) 10th ed. Table 7-4. Pg Risk Factors – Precursor lesions • Precursor lesions  Localized morphologic changes in epithelial tissue that increase the risk of malignant transformation • Could be hyperplasia, metaplasia, or dysplasia  Hyperplasia – increase in number of normal cells • Eg. Endometrial hyperplasia increases risk of endometrial cancer • Likely due to exposure to trophic factors; chronic estrogen exposure  Metaplasia – replacement of one differentiated somatic cells with another  Dysplasia – presence of abnormal cells • Eg. Cervical dysplasia increases risk of cervical cancer Metaplasia continued • Metaplasia is the replacement of one differentiated somatic cells with another • Occurs in response to chronic irritation so that cells can better withstand the stress • Occurs due to reprogramming of stem cells or undifferentiated mesenchymal cells found in connective tissues • Example: • Transformation of columnar epithelium to squamous epithelium in trachea of cigarette smokers Pathologic Basis of Disease(Robbins and Cotran) 10th ed. Figure 2.28. Page 61 Risk Factors Immunodeficiency • Immunodeficient patients are at an increase risk for cancer  Why? • They have a higher-than-normal incidence of chronic infection from viruses  Thus, higher risk of getting oncogenic virus that can result in mutations that can accumulate and lead to tumours Basic concept: • Increased cellular replication creates a “fertile ground” for development of malignant tumours  Repeated rounds of cell division  higher likelihood of accumulating mutations resulting in malignancy. • Preview: mutations frequently involve dysregulation of start transition of cell cycle References • Alberts et al. Molecular Biology of the Cell. Garland Science. • Betts et al. Anatomy and Physiology (2ed). OpenStax • Pathologic Basis of Disease(Robbins and Cotran) 10th ed.