Chapter 11 Cancer Epidemiology PDF

Chapter 11 Cancer Epidemiology Genetics, Epigenetics, and Tissue  Environmental-lifestyle factors and genetic factors cause cancer.  Patterns of cancer are environmental, not genetic. Genetic alterations and abnormalities drive cancer at the cell level. Factor...

Chapter 11 Cancer Epidemiology Genetics, Epigenetics, and Tissue  Environmental-lifestyle factors and genetic factors cause cancer.  Patterns of cancer are environmental, not genetic. Genetic alterations and abnormalities drive cancer at the cell level. Factors are influenced by the greater external environment.  Incidence Trends  Major cause of morbidity and mortality worldwide.  ~ 2 in 5 Canadians will develop cancer within their lifetime  Most new cancer cases are predicted to be lung, breast, colorectal, and prostate  Mortality Trends  In Canada overall death rate is decreasing.  ~ 1 in 4 Canadians will die of cancer.  In Canada lung cancer is the leading cause of cancer death.  Lung cancer death rate has dropped (especially for men) over the past 25 years.  In Utero and Early Life Conditions  Developmental plasticity Degree to which an organism’s development is contingent on its environment Histone modification and micro-RNAs  Studies: Dutch Famine Birth Cohort Diethylstilbestrol (DES)  Evidence for DNA methylation marks, in utero environments, and future phenotypes is growing  Environmental-Lifestyle Factors  Tobacco Cigarette smoking is the leading cause of death in Canada Multipotent carcinogenic mixture Linked to cancers of the lung, upper aerodigestive tract, lower urinary tract, kidney, pancreas, cervix, and uterus Linked to myeloid leukemia Secondhand smoke (ETS) contains many toxic chemicals Cigar and pipe smoking are equally harmful  Environmental-Lifestyle Factors (Cont.)  Diet Cooking of fat, meat, or protein produces carcinogenic substances Naturally occurring carcinogens associated with alkaloids or mould byproducts  Nutrigenomics Study of the effects of nutrition on the phenotypic variability of individuals based on genomic differences  Nutrition and Cancer  Many cellular processes are affected by nutrition.  May directly influence silencing of genes that should be active or activating genes that should be silent.  May alter hormonal axes, influence cellular proliferation, and affect phenotypes or expression of key genes.  Nutrition and Cancer (Cont.)  Xenobiotics Toxic, mutagenic, and carcinogenic chemicals in food Two defence systems for countering effects: Phase 1 activation Phase 2 detoxification enzymes  Nutrition and Cancer (Cont.)  Dietary components can be activated into carcinogens or can prevent cancer  Pathways to cancer affected by diet include: Cell cycle control Differentiation DNA repair Gene silencing Inflammation Apoptosis Carcinogen metabolism  Nutrition and Cancer (Cont.) B, Reprinted with permission from Nowsheen, S., Aziz, K., Tran, P.T., et al. (2014). Epigenetic inactivation of DNA repair in breast cancer. Cancer Letters, 342(3), 213-222.  Obesity  Correlates with the body mass index (BMI) Three factors are related to obesity and cancer: Insulin–IGF-1 axis Sex hormones Adipokines or adipocyte-derived cytokines Mechanism of obesity-associated cancer risks is unclear  Alcohol Consumption  Risk factor for oral cavity, pharynx, larynx, esophagus, liver, colorectum, and breast cancers  Genetic factors involved  No “safe limit” of intake Alcohol Consumption (Cont.) Adapted from Zakhari, S. (2013). Alcohol metabolism and epigenetic changes. Alcohol Research, 35, 6-16.  Physical Activity  Reduces cancer risk (breast, colon, and perhaps others) Decreases insulin and insulinlike growth factors. Decreases obesity. Decreases inflammatory mediators and free radicals. Increases gut motility. 1. Which statement is TRUE regarding environmental risk factors and the development of cancer? A. Chronic alcoholism is linked to lung cancer. B. Human papillomavirus can cause liver cancer. C. Ultraviolet radiation (UVR) is linked to breast cancer. D. Physical activity reduces the risk of breast cancer and colon cancer.  Ionizing Radiation  Emission from X-rays, radioisotopes, radon, and other radioactive sources  Exposure causes cell death, gene mutations, and chromosome aberrations  Mutations in germ cells are heritable  Increased use of diagnostic testing of concern  Radiation-Induced Cancer  Targeted effects: Chromosome aberrations, cell transformation, gene expression, alternative targets, mutagenesis in somatic cells, the biological effects that occur in nonirradiated cells, and effects on the microenvironment  Nontargeted effects: Bystander effects Genomic instability  Radiation-Induced Cancer (Cont.)  Acute, latent, and microenvironmental effects Organs with highly proliferative cells especially affected by acute radiation exposure Nontargeted radiation effects alter cell and tissue signalling Microenvironment changes Radiation-induced cancer has latent periods Usually between 5 to 10 years  Ultraviolet Radiation  Causes basal cell carcinoma, squamous cell carcinoma, and melanoma (increased incidence)  Principal source is sunlight  Ultraviolet A (UVA) and ultraviolet B (UVB)  Released TNF-α in epidermis  Produces ROS  Promotes skin inflammation and release of free radicals  Electromagnetic Radiation (EMR)  Nonionizing, low-frequency radiation  Microwaves, radar, cellphones, and power frequency radiation associated with electricity and radio waves, fluorescent lights, computers, and other electric equipment  May or may not be carcinogenic  Infection, Sexual and Reproductive Behaviour  Top cancer-causing infections Human papillomavirus (HPV) Helicobacter pylori (H. pylori) 75 to 89% of all stomach cancers Hepatitis B (HBV) Hepatitis C (HCV) HBV and HCV account for large majority of liver cancers  Human Papillomavirus (HPV)  At least 50% of sexually active people will have genital HPV during their lives Spread through skin contact; oral, vaginal, or rectal sex 150 related viruses Low risk—does not cause cancer High risk—can cause cancer  Human Papillomavirus (HPV) (Cont.) Causes five types of cancer Cervix Penis Vulva Anus Oropharynx (tongue and tonsils) 2. Change in lifestyle factors or controlling bacterial infection from Helicobacter pylori is responsible for a decrease in which type of cancer? A. Lung B. Stomach C. Leukemia D. Colorectal  Air Pollution  Particulate matter Particles and liquid droplets made up of acids, organic chemicals, metal, and dust particles Carcinogenic and causes lung cancer High proportion of mutagenic agents Primary particles Emitted directly from source (construction sites, smokestacks) Secondary particles Emitted from power plants, industries, and automobiles  Air Pollution (Cont.)  Indoor pollution Generally worse than outdoor pollution Tobacco smoke (passive) causes formation of reactive oxygen free radicals and thus DNA damage Radon gas trapped in houses forms decay products that are carcinogenic Exposures from heating and cooking sources and asbestos Inorganic arsenic  Chemical and Occupational Hazards  Present in air, soil, water, household products, toys, workplaces, and homes  Upper respiratory passages, lung, bladder, peritoneum  Substantial number of occupational carcinogenic agents: Asbestos (mesothelioma and lung cancer) Dyes, rubber, paint, explosives, rubber cement, heavy metals, air pollution, etc.