Cancer Epidemiology, Manifestations, and Treatment Chapter 10
Environmental Risk Factors Tobacco Ø Multipotent carcinogenic mixture Ø Linked to cancers of the lung, lower urinary tract, digestive tract, liver, kidney, pancreas, cervix uteri Ø Most common causative factor
Environmental Risk Factors Ionizing radiation Ø Emission from x-rays, radioisotopes, and other radioactive sources Ø Exposure causes cell death, gene mutations, and chromosome aberrations Ø Bystander effects Ø Poor gene repair Ø Changes in gap junction intercellular communication, increased connexin proteins enhance bystander effects
Environmental Risk Factors Ultraviolet radiation Ø Causes basal cell carcinoma, squamous cell carcinoma, and melanoma Ø Principal source is sunlight Ø Ultraviolet A (UVA) and ultraviolet B (UVB) Ø Melanoma occurs on skin burned and often on areas less exposed vs other skin cancers that occur on skin often exposed to sun and is tan more often than burned
Environmental Risk Factors Alcohol consumption Ø Risk factor for oral cavity, pharynx, hypopharynx, larynx, esophagus, and liver cancers Ø Cigarette/alcohol combination increases a person s risk
Environmental Risk Factors Occupational hazards Ø Substantial number of occupational carcinogenic agents Asbestos Dyes, rubber, paint, explosives, rubber cement, heavy metals, air pollution, etc. Radon
Environmental Risk Factors Diet Ø Xenobiotics Toxic, mutagenic, and carcinogenic chemicals in food, drugs Activated by phase I activation enzymes (Hepatic enzymes are responsible for the metabolism of xenobiotics by first activating them (oxidation, reduction, hydrolysis and/or hydration of the xenobiotic), Defense mechanisms Phase II detoxification enzymes then conjugate the active secondary metabolite with glucuronic or sulphuric acid, or glutathione, followed by excretion in bile or urine. Examples Compounds produced in the cooking of fat, meat, or proteins Alkaloids or mold by-products
Environmental Risk Factors Obesity Ø Correlates with the body mass index (BMI) Ø Adipose tissue is active endocrine and metabolic tissue, release cytokines
Environmental Risk Factors Obesity Ø In response to endocrine and metabolic signaling, adipose tissue releases free fatty acids Increased free fatty acids gives rise to insulin resistance and causes chronic hyperinsulinemia (increased insulin causes increase in IGF, a potent growth factor for many cell types) Correlates with colon, breast, pancreatic, and endometrial cancers
Environmental Risk Factors Physical activity Ø Reduces cancer risk Decreases insulin and insulin-like growth factors Decreases obesity Decreases inflammatory mediators and free radicals Increased gut motility
Clinical Manifestations of Cancer Pain Ø Little or no pain is associated with early stages of malignancy Ø Influenced by fear, anxiety, sleep loss, fatigue, cytokines, and overall physical deterioration Ø Mechanisms Pressure, obstruction, invasion of sensitive structures, stretching of visceral surfaces, tissue destruction, and inflammation
Clinical Manifestations of Cancer Fatigue Ø Subjective clinical manifestation Ø Tiredness, weakness, lack of energy, exhaustion, lethargy, inability to concentrate, depression, sleepiness, boredom, and lack of motivation
Clinical Manifestations of Cancer Fatigue Ø Suggested causes Sleep disturbance, biochemical changes from circulating cytokines, secondary to disease and treatment, psychosocial factors, level of activity, nutritional status, and environmental factors
Clinical Manifestations of Cancer Syndrome of cachexia Ø Most severe form of malnutrition Ø Present in 80% of cancer patients at death Ø Severe weight loss still occurs if they meet their daily calories requirements. Could be due to cytokines like TNF-a, break down fat and proteins Ø Includes: Anorexia, early satiety, weight loss, anemia, asthenia (weakness), taste alterations, and altered protein, lipid, and carbohydrate metabolism
Cachexia
Clinical Manifestations of Cancer Anemia Ø A decrease of hemoglobin in the blood Ø Mechanisms Chronic bleeding resulting in iron deficiency, severe malnutrition, medical therapies, or malignancy in blood-forming organs
Clinical Manifestations of Cancer Leukopenia and thrombocytopenia Ø Direct tumor invasion to the bone marrow causes leukopenia and thrombocytopenia Ø Chemotherapy drugs are toxic to the bone marrow Infection Ø Risk increases when the absolute neutrophil and lymphocyte counts fall Ø Most significant cause of complications and death in cancer patients
Paraneoplastic syndromes Ø Symptom complexes that cannot be explained by the local or distant spread of the tumor Ø These phenomena are mediated by humoral factors (by hormones or cytokines) excreted by tumor cells or by an immune response against the tumor. Ø most commonly present with cancers of the lung, breast, ovaries or lymphatic system (a lymphoma). Sometimes the symptoms of paraneoplastic syndromes show even before the diagnosis of a malignancy.
Cancer Treatment Chemotherapy Ø Use of nonselective cytotoxic drugs that target vital cellular machinery or metabolic pathways critical to both malignant and normal cell growth and replication Ø Goal Eliminate enough tumor cells so the body s defense can eradicate any remaining cells
Chemotherapy
Radiation Immunotherapy targeting specific cancer cell/ tissue characteristics Surgery
Side Effects of Cancer Treatment Gastrointestinal tract Bone marrow Hair and skin Reproductive tract