Cancer

CANCER

Cancer is the end product of a multistep process (carcinogenesis) that occurs over many years. The term "cancer" actually refers to numerous distinct diseases characterized by abnormal cell growth and differentiation. Cancers are categorized by the organ and/or cell of origin. For example, squamous cell carcinoma of the lung arises from pulmonary epithelial tissue, whereas adenocarcinoma of the breast arises from mammary duct epithelium. The natural history of a cancer is highly dependent on the organ and cell type from which it is derived. In addition, prognosis is influenced by the stage and histologic grade of the cancer. Staging is generally designated by the TNM (tumor, nodes, metastasis) staging system, which takes into account the size of the primary tumor(T), the extent to which local lymph nodes (glands) are involved (N), and whether or not distant metastases are present (M). The histologic grade, determined by microscopic examination of the biopsy specimen, provides an objective assessment of the degree of cellular differentiation.

INCIDENCE, PREVALENCE, AND MORTALITY

The worldwide burden of cancer is a major health problem, with more than 8 million new cases and 5 million deaths per year. The burden from cancer may be described in terms of incidence (number of new cases per 100,000 each year), prevalence (number of people at a given point in time with a cancer diagnosis), and mortality (number of cancer deaths). With few exceptions, cancer incidence, prevalence, and mortality rates are higher in industrialized countries (e.g., United States, European nations) than in developing countries (e.g., African nations, China). Incidence rates for specific cancers can be dramatically affected by the use of screening procedures to identify asymptomatic disease. This is illustrated by the dramatic increase in the incidence of prostate cancer that accompanied the introduction of prostate-specific antigen (PSA) screening in the late 1980s. Similarly, prevalence rates may be a poor index for comparing cancers, because they are dependent upon incidence, natural history, and treatment efficacy. For example, due to the relatively short life expectancy of individuals with pulmonary neoplasms, the prevalence of lung cancer is much lower than that of prostate cancer, despite the higher mortality rates associated with lung cancer. In addition to the impact of screening and natural history, prevalence rates increase as treatment improves, because therapeutic advances enable individuals to live longer following a cancer diagnosis.

Worldwide, lung cancer is the leading cause of cancer mortality, followed by stomach cancer. Smoking remains the leading preventable cause of cancer, and mortality and incidence rates of lung cancer rise and fall with smoking rates. The current trend shows a leveling off of smoking-related cancers in developed countries, possibly because of health-promotion and disease-prevention efforts. Geographical variations occur in cancer incidence and mortality, with Africa and Asia generally having lower rates than North America and Europe. However, it has been noted that differences in data collection and diagnostic practices make worldwide cancer comparisons somewhat difficult. Overall, worldwide incidence rates of breast, colon and rectum, and prostate cancers are highest in developed countries, while cancers of the cervix, mouth and pharynx, esophagus, and liver are higher in developing countries. Migration studies generally report that migrants from developing countries to developed countries adopt cancer incidence rates equivalent to those of their new country. For example, studies of Japanese and Chinese immigrants living in the United States show that their risks for prostate and breast cancers increase dramatically the longer they reside in the United States. Similar trends for increased risk are seen among African immigrants in European countries. Geographical variations in cancer incidence and mortality also exist in the United States. Each cancer site shows some variation, such as higher prostate cancer mortality rates in the South Central and southern Atlantic states, and higher breast cancer mortality rates in the northeastern states. The Atlas of United States Mortality, published by the Centers for Disease Control and Prevention, provides detailed geographic information on cancer mortality rates in the United States, and is available online at http://www.cdc.gov/nchs/data/atlasmet.pdf.

In the United States, cancer is the second leading cause of death; although there has been a slight decline in the number of people dying from cancer since 1990, with more than one-half of those who develop cancer being cured or surviving for over five years. Because cancer is many diseases, some cancers are more common and/or more curable than others. For example, although nonmelanoma skin cancer, mainly caused by overexposure to ultraviolet (UV) radiation from the sun, is responsible for the largest number of new cancer cases each year, mortality rates associated with it are low.

Incidence, prevalence, and mortality in the United States vary by cancer site, between whites and blacks, and between men and women. By order of incidence, the three most common cancers in men are prostate, lung, and colorectal; in women the three most common cancers are breast, lung, and colorectal. These cancer sites represent more than one-half of both new cases of cancer and deaths from cancer each year. Lung cancer is the leading cause of death from cancer for men and women, accounting for almost one-third of cancer deaths.

Although cancer risk increases with age, malignant diseases are an important cause of morbidity and mortality in the pediatric population. The most frequent cancers in children are leukemias, tumors of the nervous systems, lymphomas, soft-tissue sarcomas, and kidney tumors. Other than lung cancer, which increases dramatically after age forty, three out of every four deaths from cancer occur in individuals older than sixty years of age.

CAUSES OF CANCER

Environmental and lifestyle factors such as tobacco use, diet, alcohol consumption, and exposure to sunlight play a primary role in the development of the majority of cancers. In addition, exposure to occupational factors and to specific pathogens (e.g., viruses, bacteria), hormones, and radiation also contributes to cancer at particular sites. However, the question still remains as to why one person exposed to a given environmental or lifestyle risk factor develops cancer and another person does not. The importance of hereditary factors (gene-environment interactions) cannot be overemphasized in this regard. True "hereditary cancers," those attributable to specific genes that are passed from one generation to another, account for only a small proportion of cancer cases, however.

Exposure to carcinogens in tobacco smoke accounts for almost one-third of cancer cases, especially cancers of the lung, respiratory tract, esophagus, bladder, pancreas, and, most likely, cancers of the stomach, liver, and kidneys. Carcinogens found in the environment and the workplace (e.g., asbestos, benzene, vinyl chloride compounds, dyes, arsenic, petroleum products) and cancers associated with exposure to these chemicals (e.g., lung and bladder) are higher in urban areas than in rural areas. Diet also influences the risk of cancer, although researchers are unsure of the mechanisms involved. In general, evidence supports an increased risk of various cancers (e.g., colon, rectum) with a high intake of red meats, and a decreased risk of various cancers (e.g., lung, colon, stomach) with a high intake of vegetables and fruits. Other food constituents, such as vitamins and minerals, are also being investigated for their ability to prevent cancer.

Other possible causes of cancer include pathogens, such as hepatitis B and C viruses in liver cancer, and the Helicobacter pylori bacterium in stomach cancer. Hormonal factors contributing to cancer have focused on estrogen, progesterone, and testosterone, and their role in reproductive organ cancers. These steroid hormones are being investigated because they influence the growth of cells, particularly those of the prostate, ovary and cervix, and breast. Radiation exposure, especially UV radiation from the sun, is a significant contributor to cancer of the skin, and using sunscreens has been shown to reduce skin cancer risk.

Interactions between genes and environmental exposures are of great importance in determining one's risk of developing cancer. For instance, genes and nutrients can interact to increase or decrease the risk of cancer depending on genetic variations known as polymorphisms—different forms of the same gene that may either increase or decrease the risk of cancer. For example, different polymorphisms in the gene that determines how vitamin D is metabolized can influence the risk of prostate cancer; one polymorphism is associated with increased risk of prostate cancer and another is associated with decreased risk. Polymorphisms in the genes that are responsible for repairing radiation damage to skin cells also play a role in increasing or decreasing cancer risk.

CANCER PREVENTION AND TREATMENT

Many cancer risk factors are avoidable. Preventing cancer by attention to diet and by quitting or never starting smoking are the most significant strategies to reduce cancer risk. Prevention of cancer is being investigated in clinical trials on dietary patterns (high intake of vegetables and fruits; low intake of saturated fats) and dietary constituents such as vitamins, minerals, and soy. Future progress may depend partly on strategies such as chemoprevention—the use of natural or synthetic substances to prevent cancer cells from forming, progressing, or recurring. For example, the antiestrogen hormone tamoxifen has been shown to reduce the risk of developing breast cancer by 50 percent among women at high risk for this disease. It also has been shown to reduce the risk of developing a new primary breast cancer in the opposite breast among women with a history of breast cancer. Chemopreventive agents also are being investigated for prevention of colon, rectum, prostate, and lung cancers.

SCREENING AND EARLY DETECTION

Mammography has been shown to reduce breast cancer mortality among women over the age of fifty, and Pap smear screening has dramatically reduced mortality from cervical cancer. In addition, there is growing evidence that fecal occult blood testing and endoscopic screening significantly reduce mortality from colorectal cancer. Identification of mutations is becoming an important tool for identifying individuals at high risk of various cancers. For instance, DNA repair-gene mutations (e.g., MSH2, PMS1) have been associated with a higher risk of colon cancer, as have mutations in the tumor suppressor genes BRCA1 and BRCA2 in breast cancer. Although it is believed that inherited risk for cancer accounts for a small proportion of total cancer cases each year, identifying this risk may help researchers determine how cancer develops and progresses, and may provide a tool for targeting prevention or treatment strategies.

Prognosis is dependent on the type of cancer diagnosed, the stage of the disease at the time of diagnosis, and the effectiveness of currently available therapy. Surgery, radiation, chemotherapy, hormonal therapy, and immunologic therapy form the basis of modern cancer treatment. Surgery is generally the treatment of choice for localized tumors, although radiation often is an appropriate alternative. Lasers are being used for small noninvasive tumors of the skin, cervix, and throat. Radiation therapy is often recommended as primary therapy (e.g., for Hodgkin's disease and early stage tumors of the head and neck), and is an important adjunct to lumpectomy for the treatment of breast cancer. Radiation therapy also plays an important role in the symptomatic management of patients with advanced cancer (e.g., bone or brain metastases). In contrast to surgery and radiation, chemotherapy is a systemic, rather than local, therapy, because the drugs are distributed throughout the body. Chemotherapy generally is required to treat advanced cancers that are not amenable to surgical removal or radiation therapy. Chemotherapy is often used after surgery (adjuvant therapy) to reduce the risk of relapse. The most common indication for adjuvant chemotherapy is following surgery for localized breast or colorectal cancer.

Hormone therapy represents a very important category of cancer treatment for breast cancer (tamoxifen and raloxifene) and prostate (androgen blockers) cancer. In addition, immunotherapy (also called biologic therapy) is being used to boost the immune system to fight cancer cells. Monoclonal antibodies are one type of immunotherapy that can be used to fight specific cancer cells or to carry chemotherapeutic agents to a tumor. Interferon is another immunotherapy that has shown promise in slowing the growth of tumors. Each of these treatments has advantages and disadvantages, and should be discussed with a physician.

CANCER IN DEVELOPING COUNTRIES

Cancer trends are of great concern to the public health community. As developing countries become more industrialized, incidence and mortality rates for cancers of the breast, colon, rectum, and prostate begin to rise. Also, smoking is increasing worldwide—along with lung cancer incidence and mortality rates. Liver cancer shows the same trends as lung cancer, but for a different reason. Infection with the hepatitis B or C viruses is a major risk factor for liver cancer. In some countries, where a vaccine for hepatitis B is widely used to vaccinate infants, liver cancer incidence in later life has declined; however, incidence rates in developing countries, where vaccination is not widely available, appear to be increasing. Another virus, the human papillomavirus (HPV), is an important risk factor for cervical cancer. Cervical cancer and HPV are more common in equatorial countries (e.g., in Latin America, sub-Saharan Africa, and Southeast Asia) and less common in countries in northern latitudes. Screening and treatment for early stages of cervical cancer have made significant inroads for reducing the incidence and mortality of this disease.

HOWARD L. PARNES

DARRELL ANDERSON

(SEE ALSO: Breast Cancer; Carcinogen; Cervical Cancer; Colorectal Cancer; Environmental Determinants of Health; Environmental Tobacco Smoke; Genetics and Health; Geography of Disease; Geriatrics; Incidence and Prevalence; Lung Cancer; Melanoma; Mortality Rates; Nutrition; Occupational Safety and Health; Oral Cancer; Ovarian Cancer; Prevention; Preventive Health Behavior; Prostate Cancer; Screening; Skin Cancer)

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