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Incidence & Mortality Rates
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Cancer is the second overall leading cause of death (after ischemic heart disease) in the United States: It causes approximately 500,000 deaths annually (25% of all deaths). The incidence continues to rise, probably reflecting the increasing average age of the population.
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There are many reasons why the incidence of cancer varies tremendously in different populations and different areas. Epidemiologic study of cancer distribution often sheds light on the etiologic factors. Thorough knowledge of the incidence and pattern of cancer in the local population is important for the clinician evaluating the possibility of cancer in a given patient.
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Both the incidence (Figure 17-6) and the death rate (Figure 17-7) of cancer must be considered. The latter reflects both the incidence and the success of diagnosis and therapy. For instance, skin cancer is by far the most common cancer in the United States (> 500,000 cases per year) but is usually diagnosed early and cured by excision; the death rate from skin cancer is thus low and does not figure prominently in the overall cancer death rate statistics. (Note that in Figures 17-6 and 17-7 skin cancer other than melanoma has been specifically excluded and does not appear in the overall cancer incidence statistics.)
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Major Factors Affecting Incidence
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The presence or absence of any of the many factors influencing the incidence of cancer must be established during history taking and physical examination of a patient thought to have cancer.
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Prostate cancer in men and uterine cancer and breast cancer in women are obviously sex-specific. In other types of cancer, the reasons for the difference in incidence between the sexes are less evident. For example, cancer of the oropharynx, esophagus, and stomach is more than twice as common in men, but cancers of the gallbladder and thyroid and malignant melanoma are more frequent in women. Both bladder and lung cancer are more common in men, partly because of greater occupational exposure (dye and rubber industries for bladder cancer, mining and asbestos for lung cancer) and smoking habits. Recent figures show that the rate of lung cancer in women is fast approaching that in men as smoking habits of women match those of men (in the United States but not everywhere).
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The frequency of occurrence of most types of cancer varies greatly at different ages.
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Carcinoma is rare in children, but some leukemias, primitive neoplasms (blastomas) (Figure 17-4) of the brain, kidney, and adrenal, malignant lymphomas, and some types of connective tissue tumors are relatively common (Table 17-6). Most of these childhood neoplasms grow rapidly and are composed of small, very primitive cells with large, hyperchromatic nuclei, scant cytoplasm, and a high mitotic rate.
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In adults, carcinomas make up the largest group of malignant tumors; they result from neoplastic change occurring in mature adult-type epithelial tissues. Sarcomas occur in adults but are less common than carcinomas.
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Neoplasms of the hematopoietic and lymphoid cells (leukemias and lymphomas) occur at all ages. The incidence of different types of these neoplasms varies with age; acute lymphoblastic leukemia is common in children, whereas chronic lympho-cytic leukemia occurs more often in the elderly (Chapter 26: Blood: III. the White Blood Cells).
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Occupational, Social, and Geographic Factors
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Occupational factors have been mentioned with reference to an increased risk of bladder cancer in workers in the dye industry and lung cancer in certain miners. These aspects are discussed more fully in Chapter 18: Neoplasia: II. Mechanisms & Causes of Neoplasia and usually correlate with increased exposure to carcinogens. Because the risk is so high in certain industries, an occupational history is an essential part of a full medical examination.
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Similarly, such social habits as cigarette smoking (lung cancer)—and to a lesser extent pipe and cigar smoking, snuff taking, and tobacco chewing (cancer of the oropharynx)—represent risk factors for development of several types of cancer, and the physician must evaluate the amount of exposure to these factors during history taking.
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Epidemiologic studies also show that a patient's sexual and childbearing histories are important. Women who have borne several children and have breast-fed them have a significantly lower incidence of breast cancer than women who elect not to breast-feed or who are nulliparous. (Nuns have a high incidence of breast cancer.) Conversely, nuns have a lower incidence of cervical cancer, which appears to be most common among women who begin sexual activity early—particularly those with multiple partners. Circumcised men have a much lower incidence of carcinoma of the penis than their uncircumcised counterparts, and some studies have suggested that carcinoma of the uterine cervix is more common in women whose sexual partners have not been circumcised. Various explanations include the finding that smegma is carcinogenic in mice; associations of cervical carcinoma with standards of sexual hygiene and herpesvirus and papovavirus infections (Chapter 53: The Uterus, Vagina, & Vulva) have also been reported.
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Geographic variations in the overall incidence of cancer and in the incidence of specific types of cancer also occur from one country to another (Table 17-7), from one city to another, and from urban to rural areas (Figures 17-8 and 17-9). Detailed epidemiologic case control studies have sometimes uncovered associations with high-risk occupations, diet, environmental carcinogens, or endemic viruses; other occurrences remain unexplained. For example, the high incidence of stomach cancer in Japan (Figure 17-8) has been related to diet (smoked raw fish). This type of cancer does not appear to be genetically determined, because Japanese emigrating to the United States show within a single generation the lower incidence of stomach cancer demonstrated by native-born Americans. However, marked differences in the mortality rate of stomach cancer exist even within different parts of the United States for unknown reasons. (Areas with high gastric cancer mortality death rates in the north central United States are associated with populations of northern European descent.) The factors involved clearly differ from those playing a role in lung cancer, because the distribution of deaths due to this disease is very different, although there is some association with asbestos exposure in mining or shipyards.
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Marked variation in cancer incidence in different countries has in some cases provided important clues to the possible causative role of viruses and immune stimulation. The distribution of Burkitt's lymphoma, infection with Epstein-Barr virus, and malaria in Africa provides the best-known example of an association between a neoplasm and infection. A close association also exists between liver cell carcinoma and the incidence of hepatitis B virus carriers in a population (Figure 17-9).
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A few cancers have a simple pattern of genetic inheritance (Chapter 18: Neoplasia: II. Mechanisms & Causes of Neoplasia)—and those that do are so striking that they warrant careful study of relatives of known cases (eg, retinoblastoma, polyposis coli and carcinoma of the colon, medullary carcinoma of the thyroid).
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For other cancers, the genetic link is not as strong (eg, breast cancer) or is almost nonexistent (eg, lung cancer). It must also be understood that familial occurrence of neoplasms may represent the action of similar environmental factors rather than a genetic predisposition.
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Cancer families with a high incidence of cancer have also been described. In such cases the cancer is usually of a particular type but may be of different types; colon, endometrial, and breast cancer occur in some families. Cancer in such families may skip generations, suggesting the possible interplay both of recessive genetic mechanisms and of environmental factors.
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History of Associated Diseases
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Perhaps the most important finding in the history of a patient with suspected cancer is a record of diagnosis or treatment of previous cancer. A positive history of cancer greatly increases the chances that the current illness represents either a metastasis (which may be delayed many years) or a second primary tumor. Statistics show that patients who have had cancer—even if the lesion was totally excised—have a much higher incidence of a second cancer, particularly in the same tissue. For example, cancer in one breast increases the chances of cancer in the opposite breast, and one occurrence of colon cancer necessitates repeated routine examinations to detect the development of another colon cancer. Second cancers of a different type—particularly leukemia and sarcomas—also occur as a complication of chemotherapy and radiation used to treat the first cancer.
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In addition, certain disorders that in themselves are nonneoplastic carry an associated higher risk of development of cancer and are considered preneoplastic diseases. These diseases are uncommon, but together they constitute a significant group of risk factors (Table 17-8).
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Trends in Cancer Incidence
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The relative incidence of different types of cancer and their mortality rates vary over time and reflect both changes in incidence of various cancers and improvement in diagnosis and therapy, respectively (Figures 17-10, 17-11, 17-12, and 17-13).
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