Introduction - Colorectal cancer (CRC) is a common and lethal disease. The risk of developing CRC is influenced by both environmental and genetic factors. Approximately 145,290 new cases of large bowel cancer are diagnosed each year in the United States, of which 104,950 are colon and the remainder rectal cancers. In the U. S. more than 56,000 will die in 2005 of CRC. In the United States, CRC ranks second to lung cancer as a cause of cancer death, and it is third in frequency and cause of cancer death, in men and women, separately.
Incidence - Age is a major risk factor for sporadic CRC. It is a diagnosis after the age of 40, the incidence begins to increase significantly between the ages of 40 and 50, and age-specific incidence rates increase in each succeeding decade thereafter. The lifetime incidence of CRC in patients at average risk is about 5 percent, with 90 percent of cases occurring after age 50. The incidence is higher in patients with specific inherited conditions that predispose them to the development of CRC. These inherited conditions would include, Hereditary nonpolyposis colorectal cancer (Lynch syndrome I and II), Familial adenomatous polyposis, and a Personal or family history of sporadic cancers or adenomatous polyps. Other risk factors include inflammatory bowel disease (Ulcerative colitis, and Crohn's disease), Diabetes mellitus and Insulin resistance, Cholecystectomy, Alcohol, cigarette smoking, ureterocolic anastomosis, and prior pelvic irradiation.
Protective Factors - In addition to the risk factors for colorectal cancer described above, certain protective factors have been identified. These include a diet high in fruits and vegetables, regular physical activity, the regular use of aspirin or anti-inflammatory drugs (NASIDS), and hormone replacement therapy in postmenopausal women.
Diet - Many epidemiologic studies have shown an association between the intake of a diet high in fruits and vegetables and protection from colorectal cancer. Whether this protective effect is due to the fiber, antioxidant vitamins, folic acid, minerals such as selenium, other micronutrients, or phytochemicals (flavones) in vegetables or is due to some other constituent(s), is not known. Some reports suggest that a diet low in red meat, animal fat, and/or cholesterol may also be protective. Large epidemiologic studies have found an increased risk of distal colon cancer with long-term consumption of re meat or processed meats, while other studies (with shorter follow-up periods) have failed to find a significant relationship between meat intake and risk of colorectal cancer.
Fiber - A number of laboratory, nutritional and epidemiologic studies have identified a role of dietary fiber in the pathogenesis of CRC. However, the degree to which dietary fiber protects against the development of CRC is uncertain since discordant results have been published in a growing number of studies. A recent large study did show a protective effect; with the authors concluding that in populations with low average intake of dietary fiber, an approximate doubling of total fiber intake from foods could reduce the risk of CRC by 40 percent.
Folic acid - Data from animal and human studies have demonstrated that folic acid inhibits pathogenesis of cancer in a number of issues including the colon. The Nurses' Health study provided observational evidence in support of a protective effect from folic acid supplementation: women who used multivitamins containing folic acid (400 ug/day) significantly reduced their chance of developing CRC.
Calcium - Another possible protective factor is increased dietary calcium or calcium supplementation. Again in the Nurses' Health Study, and the Health Professionals' follow-up study, with both groups combined, higher calcium intake (>1250 mg daily versus =500 mg daily) was associated with a significant reduction in the risk of distal colon cancers, but not proximal cancers.
Magnesium - Animal studies suggest that dietary magnesium may influence CRC development. A population based study from Sweden found an inverse association between magnesium intake and the risk of CRC in women. Compared with women in the lowest quintile of magnesium intake, the risk was reduced by approximately 40 percent in women with the highest quintile of intake. This inverse association was observed for both colon and rectal cancer.
Physical activity - Substantial observational data suggest that regular exercise, either occupational or leisure time, is associated with a decreased incidence of CRC. The mechanism for the apparent protective effect of physical activity is not known.
Aspirin and NSAIDs - A substantial body of evidence supports a protective effect of aspirin and other nonsteroidal anti-inflammatory drugs on the development of colon cancer. A benefit may also be observed with other NSAIDs. How long-term aspirin or NSAID therapy might protect against colon cancer is not well understood. Proposed explanations are increased apoptosis and impairment of tumor cell growth by inhibition of cyclooxygenase-2. A very recent study suggested that it would take high doses of aspirin to get a reduction of colon cancer, but this can be associated with a risk of increased gastrointestinal bleeding.
Hormone replacement therapy - In the largest epidemiologic study (the Women's Health Study), in women taking combined postmenopausal hormone therapy the risk was reduced by almost 40 percent. However in other studies no benefit was identified.
Statins - Preliminary evidence suggests the possibility that HMG-CoA reductase inhibitors (statins) may have a protective effect against several cancers, including colon cancer, although the data are conflicting. In experimental animal models, statins reduce carcinogen-induced colon cancer by up to 65 percent, and they induce apoptosis in colorectal cancer cell lines. Moreover, a modest reduction in the incidence of colon cancer was observed in two large clinical trials evaluating the benefit of pravastatin and simvastatin for coronary artery disease.
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