Understanding what causes cancer is a complex process. Cancer has been linked to many factors, such as environmental exposures, lifestyle practices, medical interventions, genetic traits, viruses, familial susceptibility, and aging. Cancer is most probably the result of interactions between repeated carcinogenic exposures and an individual's susceptibility status (Fraumeni, 1982).
In 1941, Rous and Kidd described a possible mechanism for the development of cancer called the Initiation-Promotion-Progression Theory. This theory describes cancer development in terms of requiring multiple steps or events. In this theory, a single exposure, event, or trait would not be sufficient for the development of cancer. The first component of this theory is the Initiation Stage. The initiation stage of carcinogenesis occurs when DNA is damaged or altered. This alteration may occur through exposure to a carcinogen, or errors in DNA replication and repair. Examples of initiators include environmental hazards, such as ionizing and non-ionizing radiation, and biological factors, such as hormones and viruses. The damaged or initiated cell will not necessarily become cancerous unless it is subsequently exposed to one or more promoting agents during the Promotion Stage. Promoting agents cause the altered cells to grow, proliferate, and develop into tumors. Promoters include environmental pollutants, drugs, and hormones. Interestingly, even the biological changes of the promoters are reversible through lifestyle factors that include diet, hormones, and a healthy immune system (McCance & Roberts, 1998). The remainder of this section will discuss the primary risk factors that appear to be involved in the initiation or promotion of various cancers.
Environmental exposures and lifestyle practices have been determined to be the major risk factors in the development of cancer (Lichtenstein, et al., 2000, Chlebowski, 2000, McCance & Roberts, 1998, Fraumeni, 1982). The major lifestyle factors that contribute to cancer include smoking, alcohol, diet, medical practices, and ultraviolet exposures. As smoking is a major risk factor for both heart disease and cancer, tobacco exposure is the single largest preventable cause of early death (American Cancer Society, 2000, ACSM, 1998, McCance & Roberts, 1998, Sternfeld, 1992). More than 30% of all cancer deaths are directly related to smoking (American Cancer Society, 2000). Although smoking is most commonly associated with lung cancer, it also causes a three-fold increase in urinary tract cancers and is an established cause in cancers of the bladder, pancreas, larynx, mouth, and esophagus (Zeegers, et al., 2000 Marcus, et al., 2000, McCance & Roberts, 1998).
Alcohol consumption has been linked to increased rates of cancer in the upper respiratory tract, digestive tract, breast, colorectum, and liver (Corrao, et al, 1999). The mechanisms for increased rates of breast cancer from alcohol consumption are unclear but may be related to impairments in the immune function or the inability of the liver to clear the body of carcinogens, or from decreases in cell membrane permeability in the breast (Rohan & McMichael, 1988). For colorectal cancers, alcohol consumption has been shown to increase rectal cell proliferation or growth in the rat. This increase in the proliferation of rectal cells from alcohol exposure may be the mechanism involved in the promotion of colorectal cancers. Alcohol combined with tobacco usage has also been shown to contribute to increased rates of cancer in the mouth, pharynx, larynx, esophagus, and liver (McCance & Roberts, 1998, Fraumeni, 1982).
Dietary practices and obesity have been linked to certain types of cancer. High consumption of dietary fat is being examined as a contributing factor to endometrial, breast, prostate, ovarian, and rectal cancers (McCance & Roberts, 1998). Not all of the mechanisms for these associations are clear. High consumption of dietary fat may increase bile acids and cholesterol metabolites that may increase carcinogens in the body that are associated with colorectal cancers. Diets low in fiber have also been linked to increased rates of colon cancer. Food additives and food preparation are also suspect as cancer-causing agents. Nitrates, salts, and saccharin have been investigated as possible carcinogenic substances. Saccharin has not been shown to increase cancer risk in humans; however, this is not the case for nitrates and salts. Nitrates and salts that are used to preserve foods appear to increase rates of glandular stomach cancers. There are high rates of stomach cancers in countries where large quantities of salted fish or similarly preserved foods are consumed (McCance & Roberts, 1998). Methods of food preparation may also increase cancer rates. Excessively smoked or broiled fish or meat, or repeatedly reused fats for frying foods release Benzo(a)pyrene and other polycyclic hydrocarbons that may potentially cause cancer (McCance & Roberts, 1998). Dietary guidelines associated with lowering the risk of cancer include increasing the use of fiber, fruit, and vegetables in the diet, limiting alcohol consumption, and limiting foods that contain preservatives, or foods that are grilled or blackened (American Cancer Society, 2000).
Obesity caused by a sedentary lifestyle and/or a high consumption of dietary fat appears to contribute to an increased risk for cancers of the breast, the ovaries, and the endometrium in females (National Heart, Lung, and Blood Institute, 2000, Wu, et al., 1999). Obese females have higher numbers of fat cells, and fat cells produce estrogen. Since higher levels of estrogen have been associated with higher levels of endometrial, ovarian, and breast cancers, it has been suggested that higher levels of estrogen from increased numbers of fat cells in obese females may increase their cancer risk (McTiernan, 2000).
Medical practices and drugs have also been linked to increases in cancer rates. Androgen -anabolic steroids used to promote athletic performance and prevent muscle wasting cause cancers in the liver, prostate, and breast (Conway, et al., 2000; Fraumeni, 1982). Estrogen replacement medications and steroid contraceptives may contribute to increased risk for developing cancers of the endometrium, vagina, ovaries, and breast (Coughlin, et al., 2000; Koukoulis, 2000; McCance & Roberts, 1998). Immunosuppressants, such as those used in transplant procedures, are linked to lymphomas, skin cancer, and soft tissue sarcomas. Interestingly, some chemotherapeutic drugs used to treat cancer, such as alkylating agents, are linked to cancers of the bladder and to leukemia (McCance & Roberts, 1998). In situations where long-term prognosis is a factor, the benefits must be weighed against the risks when choosing to use these drugs.
Environmental factors that may increase cancer rates include air and ground pollution, occupational hazards, ultraviolet radiation, and radon gas. Air and ground pollution caused by industrial emissions and insecticides are associated with a variety of cancers (Ojajarvi, et al., 2000, McCance & Roberts, 1998, Fraumeni, 1982). Arsenic from pesticide applications, and from mining and smelting, contaminates groundwater and causes lung, skin, and liver cancers (Ojajarvi, et al., 2000). Industrial glues and varnish, as well as benzene byproducts from the petroleum industry, may contribute to increases in leukemia (McCance & Roberts, 1998; Fraumeni, 1982). Asbestos, mustard gas, heavy metals, aromatic hydrocarbons, and halogenated organic compounds from water chlorination are associated with increases in lung, bladder, liver, and pancreatic cancers (Ojajarvi, et al., 2000; McCance & Roberts, 1998). Radon gas trapped in houses contributes to an estimated 10% of lung and larynx cancers (Lubin et al., 1997; Tirmarche, 1997). Increases in ultraviolet exposures from tanning lamps and from diminished ozone levels contributes to increases in skin cancers and melanomas (Swerdlow, et al., 1998). Highway maintenance workers and roofers exposed to bitumen fumes and coal tar fumes from asphalt are at increased risk for cancers of the lung, stomach, and skin, as well as leukemia (Partanen & Boffetta, 1994).
Although environmental factors are the major cause of cancer, age is the single best predictor of the risk of developing cancer (American Cancer Society, 2000). Rates for the development of cancer begin to increase at 40 years of age and then increase rapidly at 50 years of age (American Cancer Society, 2000; Pfalzer, 1994; Pfalzer, 1992). The increasing risk for developing cancer with aging may be related to the increased likelihood of cumulative effects from environmental exposures, the potential for long latency periods, and increased opportunities for multi-stage processes to occur with aging (McCance & Roberts, 1998; Fraumeni, 1982).
Genetic or inherited cancers and familial susceptibility contribute to only a small percentage of cancers (McCance & Roberts, 1998; Fraumeni, 1998). A primary cause of cancer is damage to a specific gene. If the damaged gene is part of the genetic line, then the cancer can be inherited by succeeding generations. However, if the damaged gene is a somatic or general body cell, as most cancers appear to be, then the cancer will not be passed to future generations. The genetic or inherited cancers can be passed along through autosomal dominant, autosomal recessive, and X-linked transmission. Examples of inherited cancers include familial breast cancer, familial polyposis of the colon, adenomas of the colon, retinoblastomas (a childhood cancer of the eye), Wilms tumor (a childhood cancer of the kidney), and neurofibromatosis (McCance & Roberts, 1998).
The mechanisms involved in familial susceptibility for cancer are less well understood than those for inherited or genetic cancers. Cancers that tend to run in families include breast, colorectal, and prostate cancers. The impact of the environment in determining whether an individual with a familial susceptibility for cancer will actually develop cancer is not fully understood at this time. Most researchers believe that lifestyle and environmental factors markedly influence whether a person with a familial susceptibility for cancer will develop cancer (Lichtenstein, et al., 2000; McCance & Roberts, 1998; Fraumeni, 1982). Therefore, even when there is increased familial susceptibility for certain cancers, a person can modify his or her risk for developing cancer by changing environment or lifestyle practices.
Cancer also can be caused by a virus. Oncogenic viruses infect normal cells and cause alterations in the cell's genetic material. These genetic alterations can cause specific types of malignant and benign cancers in susceptible individuals by allowing uncontrolled growth in cells. Oncogenic viruses can affect DNA or RNA. Oncogenic viruses that affect DNA can cause cancers in the cervix, liver, anogenital area, mouth, larynx, nasal and paranasal tissues, and conjunctival tissues (McCance & Roberts, 1998). Oncogenic viruses that affect the RNA can cause Human T-cell leukemia. Interestingly, infection by an oncogenetic virus does not necessarily lead to the development of cancer. In some industrial regions, the Epstein-Barr virus, which causes Burkitt lymphoma, nasopharyngeal cancer, and B-cell lymphoma, has an infection rate of up to 90% of the young adult population; however, low numbers of infected individuals in these areas develop cancer (McCance & Roberts, 1998).