Cancer Epidemiology Chapter 12 Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.

2 Gene-Environmental-Lifestyle Interaction Environmental-lifestyle factors Environmental-lifestyle factors Cigarette smoking, excessive alcohol consumption, poor diet, lack of exercise, excessive sunlight exposure, sexual behavior (creates exposure to viruses), radiation, hormones, drugs, viruses, bacteria, pesticides, other environmental chemicals present in air, water, food, soil, and the workplace Cigarette smoking, excessive alcohol consumption, poor diet, lack of exercise, excessive sunlight exposure, sexual behavior (creates exposure to viruses), radiation, hormones, drugs, viruses, bacteria, pesticides, other environmental chemicals present in air, water, food, soil, and the workplace Epigenetic changes coupled with genetic changes and environmental-lifestyle factors cause the development of cancer Epigenetic changes coupled with genetic changes and environmental-lifestyle factors cause the development of cancer Changes are mitotically and meiotically heritable Changes are mitotically and meiotically heritable

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 3 Epigenetics Changes in the phenotype (appearance) or gene expression caused by mechanisms other than changes in the underlying DNA sequence Changes in the phenotype (appearance) or gene expression caused by mechanisms other than changes in the underlying DNA sequence Modifiable by lifestyle Modifiable by lifestyle Especially diet and pharmacological interventions Especially diet and pharmacological interventions

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 4 Epigenetics Methylation Methylation Addition of methyl group (CH3) to cytosine ring Addition of methyl group (CH3) to cytosine ring Aberrant methylation can lead to silencing of tumor-suppressor genes Aberrant methylation can lead to silencing of tumor-suppressor genes Histone modifications Histone modifications Histone acetylation, alterations in chromatin Histone acetylation, alterations in chromatin MicroRNAs (miRNAs) MicroRNAs (miRNAs) Small RNA molecules Small RNA molecules Target gene expression posttranscriptionally Target gene expression posttranscriptionally Act as oncogenes or tumor-suppressor genes Act as oncogenes or tumor-suppressor genes

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 5 Genetics Parental exposure prior to conception Parental exposure prior to conception In utero exposure In utero exposure Nutrition, toxins, stressors, lifestyle Nutrition, toxins, stressors, lifestyle Exposure to toxins in breast milk after birth Exposure to toxins in breast milk after birth Gene-environment interactions Gene-environment interactions

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 6 Environmental Risk Factors Tobacco Tobacco Multipotent carcinogenic mixture Multipotent carcinogenic mixture Linked to cancers of the lung, lower urinary tract, aerodigestive tract, liver, kidney, pancreas, cervix uteri, and myeloid leukemia Linked to cancers of the lung, lower urinary tract, aerodigestive tract, liver, kidney, pancreas, cervix uteri, and myeloid leukemia

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 7 Environmental Risk Factors Diet Diet Xenobiotics Xenobiotics Toxic, mutagenic, and carcinogenic chemicals in food Toxic, mutagenic, and carcinogenic chemicals in food Activated by phase I activation enzymes Activated by phase I activation enzymes Defense mechanisms Defense mechanisms Phase II detoxification enzymes Phase II detoxification enzymes Examples Examples Compounds produced in cooking fat, meat, or proteins Compounds produced in cooking fat, meat, or proteins Alkaloids or mold byproducts Alkaloids or mold byproducts

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 8 Environmental Risk Factors Obesity Obesity Correlates with the body mass index (BMI) Correlates with the body mass index (BMI) Adipose tissue is active endocrine and metabolic tissue Adipose tissue is active endocrine and metabolic tissue In response to endocrine and metabolic signaling, adipose tissue releases free fatty acids In response to endocrine and metabolic signaling, adipose tissue releases free fatty acids Increased free fatty acids give rise to insulin resistance and cause chronic hyperinsulinemia Increased free fatty acids give rise to insulin resistance and cause chronic hyperinsulinemia Correlates with colon, breast, pancreatic, and endometrial cancers Correlates with colon, breast, pancreatic, and endometrial cancers

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 9 Environmental Risk Factors Alcohol consumption Alcohol consumption Risk factor for oral cavity, pharynx, hypopharynx, larynx, esophagus, and liver cancers Risk factor for oral cavity, pharynx, hypopharynx, larynx, esophagus, and liver cancers Cigarette-alcohol combination increases a persons risk Cigarette-alcohol combination increases a persons risk

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 10 Environmental Risk Factors Ionizing radiation Ionizing radiation Emission from x-rays, radioisotopes, and other radioactive sources Emission from x-rays, radioisotopes, and other radioactive sources Exposure causes cell death, gene mutations, and chromosome aberrations Exposure causes cell death, gene mutations, and chromosome aberrations Bystander effects Bystander effects Poor gene repair Poor gene repair Changes in gap junction intercellular communication Changes in gap junction intercellular communication

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 11 Ionizing Radiation: Causes Cellular Injury

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 12 Environmental Risk Factors Ultraviolet radiation Ultraviolet radiation Causes basal cell carcinoma, squamous cell carcinoma, and melanoma Causes basal cell carcinoma, squamous cell carcinoma, and melanoma Principal source is sunlight Principal source is sunlight Ultraviolet A (UVA) and ultraviolet B (UVB) Ultraviolet A (UVA) and ultraviolet B (UVB) Promotes skin inflammation and release of free radicals Promotes skin inflammation and release of free radicals

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 13 Environmental Risk Factors Electromagnetic fields Electromagnetic fields Carcinogenic? Carcinogenic? Are they, or arent they? Are they, or arent they?

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 14 Environmental Risk Factors Sexually reproductive behavior Sexually reproductive behavior Carcinogenic types of human papillomavirus Carcinogenic types of human papillomavirus High-risk HPV High-risk HPV Physical activity Physical activity Reduces cancer risk Reduces cancer risk Decreases insulin and insulin-like growth factors Decreases insulin and insulin-like growth factors Decreases obesity Decreases obesity Decreases inflammatory mediators and free radicals Decreases inflammatory mediators and free radicals Increases gut motility Increases gut motility

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 15 Environmental Risk Factors Occupational hazards Occupational hazards Substantial number of occupational carcinogenic agents Substantial number of occupational carcinogenic agents Asbestos Asbestos Dyes, rubber, paint, explosives, rubber cement, heavy metals, air pollution, etc. Dyes, rubber, paint, explosives, rubber cement, heavy metals, air pollution, etc. Radon Radon Pesticides Pesticides Toxic wastes Toxic wastes

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 16 Environmental Risk Factors Air pollution Air pollution Outdoor Outdoor Industrial emissions, arsenicals, benzene, chloroform, formaldehyde, sulfuric acid, mustard gas, vinyl chloride, and acrylonitrite Industrial emissions, arsenicals, benzene, chloroform, formaldehyde, sulfuric acid, mustard gas, vinyl chloride, and acrylonitrite Indoor Indoor Cigarette smoke, radon Cigarette smoke, radon