10 Notes

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  1. Gene-Environment Interaction
    • The frequency and consequences of genetic mutations can be altered by a number of environmental factors. The most significant factors include smoking, radiation, obesity, a few oncogenic viruses, and Helicobactor pylori (H. pylori).
    • Cigarette smoke is carcinogenic and is the most important cause of cancer.
    • Tobacco use is associated primarily with squamous and small cell carcinomas of the lung and pulmonary adenocarcinomas. It has been linked to cancers of the lower urinary tract, upper aerodigestive tract, liver, kidney, pancreas, cervix uteri, and myeloid leukemia.
    • Environmental tobacco smoke (ETS) or involuntary smoking has also been linked to lung cancer.
    • Health risks from ionizing radiation involve neoplastic diseases but also birth defects and eye maladies.
    • Presently the risks of low-dose radiation are being debated.
    • Radiation-induced damage depends on dose response, fractionation, protraction, repair mechanisms, bystander effects, and antioxidants.
    • Biologic consequences of exposure to ionizing radiation include cell death, gene mutations, and chromosome aberrations.
    • Progeny of irradiated cells can exhibit an increased death rate and loss of reproductive potential.
    • Low levels of radiation can induce bystander effects and genomic instability. Both findings appear to be associated with oxidative stress and cell-to-cell intercellular communication.
    • Ultraviolet (UV) sunlight and reactive oxygen species (ROS) (oxidative stress) are involved in skin carcinogenesis from ultraviolet light (UVL).
    • UVL causes basal cell carcinoma and squamous cell carcinoma.
    • UV radiation is now known to cause specific gene mutations.
    • Understanding dietary factors that increase the risk for cancer is complex because of the variety of foods consumed, the constituents of food, the metabolic consequences of eating, and changes in patterns of food use, and accurate recall and response.
    • Toxic carcinogenic substances include compounds produced in the cooking of fat, meat, or protein; and naturally occurring carcinogens associated with plant foods.
    • The strongest and most consistent support for diet and cancer is data related to alcohol, aflatoxin, and Chinese-style salted fish fed to infants.
    • Table 10-2 is a comprehensive table showing the relationship between dietary factors and cancer risk.
    • Obesity is linked to cancer. High BMI is associated with higher rates of death from esophageal, stomach, colorectal, liver, breast, gallbladder, pancreatic, prostate, kidney, and cervical cancers; non-Hodkin lymphoma; multiple myeloma; and leukemia.
    • Adipose tissue is active endocrine and metabolic tissue. Increase release of free fatty acids, resistin, TNF-α, and reduced release of adiponectin give rise to insulin resistance. Adipose tissue cells produce steroid-hormone-metabolizing enzymes and are in important source of estrogens in postmenopausal women. Insulin-like growth factor-1 (IGF-1) regulates cell proliferation and inhibits apoptosis and the synthesis and biologic availability of female and male sex hormones.
    • Chronic alcoholism is a strong risk factor for cancer of the oral cavity, pharynx, hypopharynx, larynx, esophagus, and liver. It is less strongly related to breast cancer and colorectal cancer; however, breast carcinogenesis can be enhanced with relatively low daily amounts.
    • Multiple mechanisms are involved in alcohol-related carcinogenesis and include acetaldehyde, induction of cytochrome P-450, and ROS, increased procarcinogen activation, cell cycle effects, and nutritional deficiencies.
    • Sexually transmitted infection with high-risk types of HPV is required for the development of virtually all cervical cancers.
    • Physical activity reduces the risk of breast and colon cancers and may reduce the risk of other cancers.
    • A substantial percentage of cancers of the upper respiratory passages, lung, bladder, and peritoneum are attributed to occupational factors.
    • Air pollution is a concern in regard to cancer because of inhalation of emissions, including arsenicals, benzene, chloroform, vinyl chloride, and acrylonitrile. Indoor pollution because of cigarette smoke and possibly radon gas.
    • The relationship between electromagnetic fields (EMF’s) and carciongenesis is controversial. The evidence does not provide clear or consistent results; however, the results cannot establish the absence of any hazard.
  2. Clinical Manifestations of Cancer
    • Clinical manifestations of cancer include pain, fatigue, cachexia, anemia, leucopenia, thrombocytopenia, and infection.
    • Pain generally is associated with the late stages of cancer. It can be caused by pressure, obstruction, invasion of a structure sensitive to pain, stretching, tissue destruction, and inflammation.
    • Key to adequate pain control is the continual evaluation of pain as reported by the individual.
    • Fatigue is the most frequently reported symptom of cancer and cancer treatment.
    • Cachexia (loss of appetite, weakness, inability to maintain weight, taste alterations, altered metabolism) leads to protein-calorie malnutrition and progressive wasting.
    • Anemia associated with cancer usually occurs because of malnutrition, long-term bleeding and resultant iron deficiency, chemotherapy, and malignancies in the blood-forming organs.
    • Leukopenia is usually a result of chemotherapy, which is toxic to bone marrow, or radiation, which kills circulating leukocytes.
    • Thrombocytopenia is usually the result of chemotherapy or malignancy in the bone marrow.
    • Infection may be caused by leucopenia, immunosuppression, or debility associated with advanced disease.
  3. Cancer Treatment
    • Cancer is treated with surgery, radiotherapy, chemotherapy, immunotherapy, and combinations of these modalities.
    • The theoretic basis of chemotherapy is the vulnerability of tumor cells in various stages of the cell cycle. The goal of chemotherapy is to eradicate enough tumor cells so that the body’s natural defenses can eradicate remaining cells.
    • Combination chemotherapy is the synergistic use of several agents. This approach helps decrease single agent drug resistance and reduce harmful effects on normal cells.
    • Ionizing radiation causes cell damage, so the goal of radiotherapy is to damage the tumor without causing excessive toxicity or damage to nondiseased structures.
    • Surgical therapy is used for nonmetastatic disease, for which cure is possible by removing the tumor, and as a palliative measure to alleviate symptoms.
    • Immunotherapy is appropriate for cancers that cannot be managed effectively by chemotherapy or radiation, usually because enough tumor cells are inactive and invulnerable to these modalities.
    • Forms of immunotherapy, such as vaccines and biologic response modifiers, include immunomodulating agents, interferons, antigens, effector cells, lymphokines, and monoclonal antibodies.
  4. Side Effects of Cancer Treatment
    • Special care is needed to address and alleviate side effects because individual compliance with therapy is directly linked to a person’s perception of discomfort and complications.
    • Key to increasing compliance is appropriate education about the side effects and treatments.
    • Most side effects are directly related to the targeting of the rapidly growing cell.
    • Both chemotherapy and radiation therapy may cause a decreased cell turnover leading to oral ulcers, malabsorption, and diarrhea.
    • Disruption of barrier defenses in the gastrointestinal tract increases risk for infection.
    • Nausea is thought to be caused by an agent’s direct action on the vomiting center in the central nervous system. Thus aggressive treatment with antiemetic therapy is mandated.
    • Chemotherapy can cause bone marrow suppression of all three cell lines, red, white, and platelets. Anemia is common with red cell suppression, decreased platelet numbers can increase bleeding, and decreased white blood cells increases the risk of infection.
    • Hair loss (alopecia) results from chemotherapy effects on hair follicles. Alopecia is usually temporary and not all agents cause it.
    • Radiation and chemotherapy may affect the gametes leading to varying degrees of decreased fertility and premature menopause. These effects are dose- and age-dependent, with the prepubertal gonad thought to be more resistant to damage.
    • Craniospinal irradiation for central nervous system tumors may affect the hypothalamus or pituitary gland resulting in gonadal failure.
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10 Notes
2012-05-01 02:29:53

Cancer Epidemiology, Manifestations, and Treatment
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