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PowerLecture: Chapter 23 Genes and Disease: Cancer Learning Objectives Understand the relationship between cancer and cellular genetic controls. Know the steps in cancer development. List the environmental factors that influence cancer development. Describe the relationship between lifestyle and cancer. Describe some of the characteristics of more well-known cancers. Impacts/Issues Between You and Eternity Between You and Eternity Cancer affects one in three people in the U.S. and kills one in four; each year more than 200,000 women are diagnosed with breast cancer alone. Some women carry the BRCA1 or BRCA2 gene, which increases the risk of developing breast cancer. Some women with elevated risk for breast cancer opt for preventive mastectomy. Diagnosed early, most cancers are treatable, and many curable. Video: Preventing Cancer Surgically This video clip is available in CNN Today Videos for Anatomy and Physiology, 2003, Volume VII. Instructors, contact your local sales representative to order this volume, while supplies last. Useful References for Impacts/Issues The latest references for topics covered in this section can be found at the book companion website. Log in to the book’s e-resources page at www.thomsonedu.com to access InfoTrac articles. Genome News Network: Breast Cancer Susceptibility Genes: Overstating the Risk? InfoTrac: Monster Tumors Show Scientific Potential in War against Cancer. Elizabeth Svoboda. The New York Times, June 6, 2006. How Would You Vote? To conduct an instant in-class survey using a classroom response system, access “JoinIn Clicker Content” from the PowerLecture main menu. Would you support legislation requiring insurers to pay for the removal of a breast that is only at risk for developing cancer? a. Yes, they should be required to pay at least in proportion to a woman's chances for developing cancer. b. No, they should pay for annual exams, but not for surgery unless cancer is actually detected. Useful References for How Would You Vote? The latest references for topics covered in this section can be found at the book companion website. Log in to the book’s e-resources page at www.thomsonedu.com to access InfoTrac articles. InfoTrac: Breast Removal: The Latest in Cancer Prevention. HealthFacts, Feb. 1999. InfoTrac: Is a 0.2% Chance of Death from Breast Cancer Worth a Bilateral Prophylactic Mastectomy? Contemporary OB/GYN, June 2005. American Cancer Society: Insurance May Not Cover Preventive Surgery for High-Risk Women Section 1 Cancer: Cell Controls Go Awry Cancer: Cell Controls Go Awry Some tumors are cancer, others are not. Overgrowth of cells in a tissue (hyperplasia) results in the formation of a defined mass called a tumor, or neoplasm. Figure 23.2 Cancer: Cell Controls Go Awry Benign tumors are often enclosed in a capsule of connective tissue. • • • The cells are organized in orderly array. The cells grow slowly and are well differentiated. Because they do not affect surrounding tissue (there are exceptions), they usually are not considered a threat to health. capsule © 2007 Thomson Higher Education Fig 23.1, p.428 Cancer: Cell Controls Go Awry Dysplasia is an abnormal change in the sizes, shapes, and organization of cells in a tissue. • • • It is often a precursor to cancer. Microscopically, the edges of the tumor look ragged and the cells are clumped. Functionally the cells have many characteristics that alter their behavior from that of normal cells. Cancer: Cell Controls Go Awry Cancer cells have abnormal structure. A cancer cell has a large nucleus, less cytoplasm, and is poorly differentiated. The cytoskeleton shrinks and becomes disorganized; proteins of the plasma membrane also become altered. Cellular division of transformed cells results in cancerous daughter cells. Cancer: Cell Controls Go Awry Cancer cells lack normal controls over cell division. In a cancerous tumor, more cells are dividing than dying, so growth continues unaffected by the usual contact inhibition provided by crowding. Cancer cells lack strong cell-to-cell junctions and so tend to move about (metastasis) and become malignant. a Cancer cells break away from their home tissue. b The metastasizing cells become attached to the wall of a blood vessel or lymph vessel. They secrete digestive enzymes into it. Then they cross the wall at the breach. c Cancer cells creep or tumble along inside blood vessels, then leave the bloodstream the same way they got in. They start new tumors in new tissues. Fig 23.3, p.429 Cancer: Cell Controls Go Awry Some cancer cells produce HCG (human chorionic gonadotropin), which can be detected in blood and which signals cancer somewhere in the body; cancer cells also produce angiogenin, which encourages new blood vessel development. Animation: Cancer and Metastasis CLICK TO PLAY Animation: Characteristics of Cancer CLICK TO PLAY Video: Fibroid Tumors This video clip is available in CNN Today Videos for Anatomy and Physiology, 2004, Volume VIII. Instructors, contact your local sales representative to order this volume, while supplies last. Useful References for Section 1 The latest references for topics covered in this section can be found at the book companion website. Log in to the book’s e-resources page at www.thomsonedu.com to access InfoTrac articles. InfoTrac: Gene Signature Helps Predict Melanoma Outcome. Diana Mahoney. Internal Medicine News, Mar. 1, 2006. Section 2 The Genetic Triggers for Cancer The Genetic Triggers for Cancer Cancer develops in a multistep process. The transformation of a normal cell into a cancerous one is called carcinogenesis. Cancer develops through a series of changes that upset normal controls over cell division. Oncogenes induce cancer when tumor suppressor genes are mutated. Proto-oncogenes are normal genes that regulate cell growth and development. POSSIBLE TRIGGERS chemical carcinogens virus normal cell radiation heredity mutation in proto-oncogenes and tumor suppressor genes remove normal growth controls abnormal cell immune system breakdown immune system activated (cytotoxic T cells and NK cells) abnormal cell proliferates abnormal cell destroyed tumor tumor cells break away; metastasis to other parts of body © 2007 Thomson Higher Education Fig 23.4, p.430 POSSIBLE TRIGGERS chemical carcinogens virus normal cell radiation heredity mutation in proto-oncogenes and tumor suppressor genes remove normal growth controls abnormal cell immune system breakdown immune system activated (cytotoxic T cells and NK cells) abnormal cell proliferates abnormal cell destroyed tumor tumor cells break away; metastasis to other parts of body Stepped Art Fig 23.4, p.430 The Genetic Triggers for Cancer Oncogenes are modified from protooncogenes; they code for altered proteins that remove the controls over cellular division. • • • Cancer cannot be caused by oncogenes alone but requires the absence or mutation of tumor suppressor genes. For example, retinoblastoma is normally suppressed by at least one gene, but if this gene is altered, the suppression is removed and cancer develops. BRCA1 and BRCA2 are also tumor suppressor genes whose disruption can lead to breast cancer. BRCA 2 BRCA 1 Chromosome 13 Chromosome 17 Fig 23.5, p.431 The Genetic Triggers for Cancer The p53 gene codes for a regulatory protein that turns on proto-oncogenes that stop cell division at the right time; its alteration removes this inhibition and allows cells to divide unchecked. An oncogene may mutate in a way that triggers expression. • • Translocation may move an oncogene away from a regulatory nucleotide sequence that normally prevents its expression. New genetic material may be introduced into a cell (as by a virus) and disrupt controls. The Genetic Triggers for Cancer There also are other routes to cancer. Inherited susceptibility to cancer. • • If a mutation occurs in a germ cell and it removes controls over a proto-oncogene, the defect can be passed on to offspring. Most instances of inherited cancer susceptibility are complicated by the fact that several genes are probably involved. Viruses. • • Viruses can become inserted into host cell DNA, possibly altering the functioning of proto-oncogenes. Viruses can also carry oncogenes and insert them into host cell DNA. The Genetic Triggers for Cancer Chemical carcinogens. • • • • Carcinogens are chemicals that can damage DNA, resulting in subsequent mutations. Some of the chemicals that cause cancer are byproducts of an industrialized society, such as asbestos, vinyl chloride, and benzene; hydrocarbons in cigarette smoke and fireplace soot; and substances in dyes and pesticides. Natural carcinogens include aflatoxin, produced by a fungus that grows on peanuts. Some chemicals may be “pre-carcinogens” that cause changes only after they have been altered by metabolic activity of the cell. The Genetic Triggers for Cancer Radiation. • • Radiation can damage DNA. Sources include UV radiation from sunlight and tanning lamps, X rays, cosmic rays, radon gas, and nuclear reactors; sun exposure is probably the greatest risk factor. Breakdowns in immunity. • • • A healthy immune system regularly detects and destroys cancer cells by means of cytotoxic T cells. The protective function of the immune system can be compromised by therapeutic drugs or even anxiety and severe depression. Sometimes, the cancer itself can suppress the immune system. Useful References for Section 2 The latest references for topics covered in this section can be found at the book companion website. Log in to the book’s e-resources page at www.thomsonedu.com to access InfoTrac articles. Cancer Backup: Retinoblastoma in Children InfoTrac: Study IDs Gene Triggers to Liver Cancer. Jamie Talan. Newsday (Melville, NY), June 28, 2006. InfoTrac: Scientists Link Gene to Metastatic Cancer. UPI NewsTrack, July 3, 2006. Section 3 Assessing the Cancer Risk from Environmental Chemicals Assessing the Cancer Risk from Environmental Chemicals According to the American Cancer Society, factors in the environment account for half of all cancers; these factors include UV light, radiation, and industrial and agricultural chemicals. Roughly 40% of the food in supermarkets in the U.S. contains pesticide residues; some of these pesticides are banned in the U.S., but come in on imports. Figure 23.6 Assessing the Cancer Risk from Environmental Chemicals More exposure comes from pesticides used in community and home spraying. The Ames test, developed by biochemist Bruce Ames, uses bacteria to test for the mutagenic potential of various chemicals. Useful References for Section 3 The latest references for topics covered in this section can be found at the book companion website. Log in to the book’s e-resources page at www.thomsonedu.com to access InfoTrac articles. InfoTrac: Science That Sticks: Chemist’s Work behind U.S. Decision to Ban PFOA. Canadian Chemical News, Mar. 2006. EPA: Carcinogens Section 4 Diagnosing Cancer Diagnosing Cancer Early and accurate diagnosis of cancer is important for maximizing the success of treatment. Figure 23.7 Diagnosing Cancer There are seven general warning signs of cancer (CAUTION): Diagnosing Cancer Various tests can be performed to confirm or rule out cancer. Blood tests can detect tumor markers, such as HCG or PSA (prostate-specific antigen). Radioactively labeled monoclonal antibodies are useful in pinpointing the location and size of certain tumors; medical imaging techniques such as MRI, X rays, ultrasound, and CT are also used to locate tumors. Diagnosing Cancer The definitive detection tool is biopsy, removal of a small piece of tissue for microscopic examination. A snippet of radioactively labeled DNA, called a DNA probe, can be used to locate gene mutations; however, it is expensive and usually not covered by insurance. Recommended Cancer Screening Tests Useful References for Section 4 The latest references for topics covered in this section can be found at the book companion website. Log in to the book’s e-resources page at www.thomsonedu.com to access InfoTrac articles. Oncology Nursing Society: Cancer Symptoms Mayo Clinic: Diagnosing Cancer InfoTrac: Early Cancer Diagnosis: Present and Future. Andre Baron et al. Patient Care for the Nurse Practitioner, Sept. 2005. Section 5 Some Major Types of Cancer Some Major Types of Cancer Cancers are named according to the type of tissue where they are first formed. Sarcomas are cancers of connective tissues. Carcinomas arise from epithelium, including skin and epithelial linings of internal organs. Cancers of glands are adenocarcinomas. Lymphomas are cancers of lymph tissue. Cancer of stem cells or bone marrow is leukemia. Some Major Types of Cancer The following conclusions are drawn from the cancer statistics in Figure 23.8. Highest cancer incidence: male—prostate; female—breast. Highest cancer deaths: both male and female— lung. Cancer Incidence by Site and Sex* MALE Cancer Deaths by Site and Sex FEMALE MALE FEMALE prostate 232,090 breast 211,240 lung and bronchus 93,010 lung and bronchus 90,490 lung and bronchus 73,020 lung and bronchus 79,560 prostate 30,350 colon and rectum 71,820 colon and rectum 73,470 colon and rectum 28,540 colon and rectum 27,750 urinary bladder 47,010 uterus 40,880 ovary 16,210 melanoma of the skin 33,580 non-Hodgkin lymphoma 27,320 pancreas 15,820 leukemia 12,540 non-Hodgkin lymphoma 29,070 melanoma of the skin 26,000 kidney 22,490 ovary 22,220 leukemia 19,640 thyroid 19,190 oral cavity 19,100 urinary bladder 16,080 pancreas 16,080 pancreas 16,100 all sites 710,040 all sites 662,870 esophagus 10,530 liver 10,330 non-Hodgkin lymphoma 10,150 breast 40,410 pancreas 15,980 leukemia 10,070 non-Hodgkin lymphoma 9,050 uterus 7,310 urinary bladder 8,970 multiple myeloma 5,640 kidney 8,020 brain 5,480 all sites 295,280 all sites 275,000 * Excludes basal- and squamous-cell skin cancer and in situ carcinomas except urinary bladder. © 2007 Thomson Higher Education Fig 23.8, p.434 Video: Fighting Sarcoma This video clip is available in CNN Today Videos for Anatomy and Physiology, 2004, Volume VIII. Instructors, contact your local sales representative to order this volume, while supplies last. Useful References for Section 5 The latest references for topics covered in this section can be found at the book companion website. Log in to the book’s e-resources page at www.thomsonedu.com to access InfoTrac articles. InfoTrac: Sarcomas Most Common Cancer Type in Teenagers. GP, April 7, 2006. InfoTrac: Mutations Point the Way to New Leukemia Drugs. Ascribe Higher Education News Service, July 17, 2006. Abramson Cancer Center: Oncolink Association of Cancer Online Resources: Types of Cancer Section 6 Treating and Preventing Cancer Treating and Preventing Cancer Chemotherapy and radiation kill cancer cells directly. Chemotherapy uses drugs to kill cancer cells. • • The cancer drugs disrupt DNA replication during S phase or prevent mitosis by inhibiting the formation of the mitotic spindle. These drugs are also toxic to rapidly growing human cells, such as hair cells, stem cells, and epithelial cells. Treating and Preventing Cancer Radiation kills both cancer cells and the healthy cells around them. Adjuvant therapy combines less-toxic chemotherapy with surgery to remove the tumor. Monoclonal antibodies are used to deliver lethal doses of radiation or anticancer drugs to tumor cells specifically. Immunotherapy is the use of substances such as interferon and interleukins to activate cytotoxic T cells to attack the cancer. Treating and Preventing Cancer Anticancer drugs may be matched to genetic characteristics of cancer cells. Traditional chemotherapy drugs were matched to the organ where the cancer occurs. New strategies aim to match therapy with the specific genetic characteristics of the cancerous cells, regardless of where the cancer occurs. Treating and Preventing Cancer You can limit your cancer risk. We cannot control heredity of some aspects of biology, but we can make choices to affect our own health. Some strategies for limiting cancer include: • • • • • • Avoid tobacco in any form. Maintain desirable weight. Eat a low-fat, high-fiber diet. Restrict alcohol intake. Avoid hazardous chemicals in the workplace. Avoid excessive sun exposure. Figure 23.9 Video: Prostate Cancer Prevention This video clip is available in CNN Today Videos for Anatomy and Physiology, 2004, Volume VIII. Instructors, contact your local sales representative to order this volume, while supplies last. Useful References for Section 6 The latest references for topics covered in this section can be found at the book companion website. Log in to the book’s e-resources page at www.thomsonedu.com to access InfoTrac articles. National Cancer Institute: Clinical Trials Cancer Research Institute InfoTrac: HPV DNA Testing and HPV Vaccines Described by Experts as Combination That Offers Best Hope of Preventing Cervical Cancer. PR Newswire, April 27, 2006. Section 7 Cancers of the Breast and Reproductive System Cancers of the Breast and Reproductive System Breast cancer is a major cause of death. Breast cancer ranks second to lung cancer as a cause of death in females. • • Causative factors include obesity, late childbearing, early puberty, late menopause, excessive estrogen, and familial history. Early detection by breast examination and mammography are keys to cure. Treatment methods include modified radical mastectomy and lumpectomy; some drugs such as tamoxifen are also used. 1. Lie down and put a folded towel under your left shoulder,then put your left hand behind your head. With the right hand (fingers flat), begin the examination of your left breast by following the outer circle of arrows shown. Gently press the fingers in small, circular motions to check for any lump, hard knot, or thickening. Next, follow the inner circle of arrows. Continue doing this for at least three more circles, one of which should include the nipple. Then repeat the procedure for the right breast. For a complete examination, repeat the procedure while standing in a shower. Hands glide more easily over wet skin. 2. Stand before a mirror, lift your arms over your head, and look for any unusual changes in the contour of your breasts, such as a swelling, dimpling, or retraction (inward sinking) of the nipple.Also check for any unusual discharge from the nipple. If you discover a lump or any other change during a breast self-examination, it’s important to see a physician at once. Most changes are not cancerous, but let the doctor make the diagnosis. Fig 23.10b, p 436 Cancers of the Breast and Reproductive System Uterine and ovarian cancer affect women. Uterine cancer rates are declining due to early detection, mainly by Pap smear. Ovarian cancer is often lethal because symptoms do not occur until the cancer is advanced; the chemical taxol has been used with moderate success. Cancers of the Breast and Reproductive System Testicular and prostate cancer affect men. Testicular cancer is painless in its early stages but may spread to the lymph nodes and eventually to the lungs; surgery is the usual treatment. Prostate cancer is second only to lung cancer in causing cancer deaths in men; a PSA blood test is diagnostic, and cure rate is high for cancers detected early. Figure 23.11 Video: Breast Cancer Treatment This video clip is available in CNN Today Videos for Anatomy and Physiology, 2003, Volume VII. Instructors, contact your local sales representative to order this volume, while supplies last. Useful References for Section 7 The latest references for topics covered in this section can be found at the book companion website. Log in to the book’s e-resources page at www.thomsonedu.com to access InfoTrac articles. InfoTrac: Tylenol Lowers Ovarian Cancer Risk. UPI NewsTrack, July 10, 2006. Section 8 A Survey of Other Common Cancers A Survey of Other Common Cancers Oral cancers occur in the lips, mouth, tongue, salivary glands, and throat and are most common among users of any form of tobacco; most of the cancers are highly deadly. A Survey of Other Common Cancers Lung cancer kills more people than any other cancer. The overwhelming risk factor is smoking, a practice that is declining in men but increasing in women. Lung cancers include squamous cell carcinomas, adenocarcinomas (large-cell carcinomas), and small-cell carcinomas. A Survey of Other Common Cancers Cancers of the stomach and pancreas are usually adenocarcinomas of the duct cells and are usually not detected until they have spread. A Survey of Other Common Cancers Most cancers of the colon and rectum (colorectal cancers) are adenocarcinomas. The cancers generally start as small polyps (growths). Warning signs include blood in the feces; a family history of colorectal cancer or inflammatory bowel disease is a major risk factor. Figure 23.12 A Survey of Other Common Cancers Urinary system cancers. Carcinomas of the kidneys and bladder are related to smoking and industrial chemicals. Wilms tumor is an inherited type of kidney cancer that appears most often in children. A Survey of Other Common Cancers Cancers of the blood and lymphatic system. Lymphomas, such as non-Hodgkin lymphoma, Hodgkin’s disease, and Burkitt lymphoma, seem to increase with infections that impair the immune system. Leukemias—cancers of the stem cells of the bone marrow—lead to overproduction of white blood cells; treatment is with chemotherapy, especially the plant derivatives vincristine and vinblastine. A Survey of Other Common Cancers Skin cancers are the most common of all cancers. Malignant melanoma, cancer of the melanocyte cells, metastasizes aggressively. Squamous cell carcinomas start out as scaly, reddened bumps that grow rapidly and can spread to adjacent lymph nodes. Basal cell carcinomas grow slowly into ulcers with beaded margins. A Survey of Other Common Cancers Basal cell carcinoma and squamous cell carcinoma are more common than malignant melanoma and can be easily treated with minor surgery. Video: Skin Sun Damage This video clip is available in CNN Today Videos for Biology, 2003, Volume VII. Instructors, contact your local sales representative to order this volume, while supplies last. Video: Custom Cancer Vaccine This video clip is available in CNN Today Videos for Anatomy and Physiology, 2003, Volume VII. Instructors, contact your local sales representative to order this volume, while supplies last. Useful References for Section 8 The latest references for topics covered in this section can be found at the book companion website. Log in to the book’s e-resources page at www.thomsonedu.com to access InfoTrac articles. InfoTrac: American Academy of Dermatology Warns of Skin Cancer Risks This Summer; More Than 1 Million New Cases of Skin Cancer to Be Diagnosed This Year in U.S. Internet Wire, July 7, 2006. Mayo Clinic: Pancreatic Cancer American Cancer Society: All About Colon and Rectum Cancer