Colorectal cancer—cancer of the colon and rectum—is the second most commonly diagnosed cancer in American men and women. Colorectal cancer develops in the digestive system, which processes food for energy and rids the body of solid waste. Together, the colon and rectum form a muscular tube about 5 feet long known as the large intestine. The colon (the first and largest part of the large intestine) absorbs water and nutrients from food and serves as a storage place for solid waste. The waste moves from the colon into the rectum (the final 6 inches of the large intestine) where it passes out of the body through the anus. Cancers affecting either of these organs are called colorectal cancer. Most colorectal cancers arise from benign polyps (abnormal masses of tissue) that begin growing on the inner lining of the colon or rectum. These growths spread very slowly, taking from 10 to 20 years to become cancerous. Once colorectal cancer is diagnosed, the prognosis depends on how far the cancer has spread.

The American Cancer Society estimates that about 130,000 cases of colorectal cancer are diagnosed every year in the United States. Most cases of colorectal cancer occur in people older than 50 years of age. Although colorectal cancer is expected to be responsible for about 56,000 deaths this year, the death rate from this form of cancer has been dropping steadily for the past 20 years. Some researchers speculate that the lowering death rate is due to prevention and early treatment of the disease.

Unfortunately, most people with colorectal cancer will not begin to experience symptoms until the disease is already at a late stage. In fact, some people may experience no symptoms at all. This is the reason that screening tests, such as a colonoscopy, are so important.

In general, signs and symptoms of colorectal cancer can include the following:

• Changes in bowel habits
• Blood in the stool
• Problems related to blood loss (anemia, weakness, fatigue, shortness of breath, pounding or racing heart, chest pain, and intolerance to exercise)
• Abdominal discomfort (frequent gas, bloating, fullness, cramps, and/or pain)
• Unexplained weight loss
• Pain with defecation
• Stools that are narrower than usual
• Urgent desire to defecate (and the passage of little matter)

These symptoms may be caused by colorectal cancer or by other conditions such as infections, hemorrhoids, and inflammatory bowel disease. It is important to bring any these symptoms to the attention of your healthcare practitioner to determine the cause of your symptoms.

Although more than half of all colorectal cancers occur without any clear cause, studies suggest that genetic factors may play an important role in the development of the disease. For example, many people with colorectal cancer carry specific genetic mutations (genes that normally suppress cancer growth are mutated and actually promote cancer growth) or have relatives with the condition. Those with a family history of specific genetic syndromes, such as familial adenomatous polyposis, Lynch syndrome, juvenile polyposis, and Peutz-Jeghers syndrome are also at an increased risk for developing colorectal cancer. Dietary and lifestyle factors, such as smoking and high-fat intake, also influence the development of colorectal cancer. Some researchers speculate that genetic factors predispose a person to colorectal cancer, but that dietary and lifestyle factors play a strong role in determining which "at-risk" individuals go on to develop the disease.

• Family history of colorectal cancer or polyps in the colon
• Older age (more than 50 years)
• Living in an industrialized country like the United States
• Polyps on the inner lining of the colon or rectum
• African-American descent
• Diets high in meat and low in fruits and vegetables
• Overweight or obesity
• Regular consumption of alcohol
• Smoking cigarettes regularly
• Inflammatory bowel disease (such as Crohn's disease and ulcerative colitis)

After obtaining a complete medical history, a healthcare practitioner will perform a physical exam and may order one or more tests to diagnose colorectal cancer. As mentioned in the Preventive Care section, standard tests used to diagnose colorectal cancer include the sigmoidoscopy, colonoscopy, and barium enema. At the time of either a sigmoidoscopy or a colonscopy, a biopsy (sample of tissue) is removed from the colon or rectum and examined under a microscope in order to detect abnormal growths. If the doctor finds cancer, a series of tests (chest x-ray, abdominal CT scan, and blood tests to check liver function) will be performed to determine if the cancer has spread and to help determine the stage (or extent) of the disease. Stages of colorectal cancer include:

• Stage A—the earliest stage; cancer is found only in the innermost lining of the colon and/or rectum
• Stage B1—involves the muscular part of the colon and/or rectum
• Stage B2 —cancer has spread to deeper layers of the wall of the colon and/or rectum
• Stage C—cancer has spread to nearby lymph nodes but not to other parts of the body
• Stage D—cancer has spread to other parts of the body, such as the liver and lungs

Screening

Colorectal cancer is highly preventable, even curable, when detected early. Regular screening for colorectal cancer helps detect the presence of polyps before they become cancerous. The American Cancer Society recommends the following standard screening practices for individuals who are not at high risk for colorectal cancer and who have no symptoms of the disease:

• Annual digital rectal exams starting at age 40—the doctor inserts a lubricated, gloved finger into the rectum to feel for abnormal areas
• Annual fecal occult blood tests starting at age 50—stool samples are tested in the doctor's office for the presence of hidden blood
• Visualization of the colon via one of the following:

Sigmoidoscopy (examination of the rectum and lower colon using a lighted instrument)

Colonoscopy (examination of the rectum and entire colon using a lighted instrument)

Barium enema (examination using a series of x-rays that reveal barium-stained outlines of the colon and rectum) every 3 to 5 years starting at age 50

Those with a family history of colorectal cancer should undergo colonoscopy every 3 to 5 years, starting at least 10 years before the age of the relative at the time of his or her diagnosis. Those with a family history of familial adenomatous polyposis (a condition causing thousands of polyps along the inner lining of the colon) or other similar genetic syndromes (listed under Causes) should start having colonoscopies at age 10.

Diet and Exercise

People can also lower their chances of developing colorectal cancer by managing the risk factors they can control, such as diet and exercise. For example, eating plenty of fruits and vegetables as well as foods rich in omega-3 fatty acids and calcium can help reduce the risk of colorectal cancer. Limiting alcohol consumption, quitting smoking, and reducing the intake of high-fat foods, particularly meat, may also protect against the development of the disease. Physical activity is another factor that people can control. Obesity and sedentary lifestyles increase the risk of colorectal cancer and even small amounts of exercise on a regular basis can be helpful. The American Cancer Society recommends at least 30 minutes of physical activity on most days.

Other Preventive Measures

Preliminary studies also suggest that aspirin may prevent tumor growth and that estrogen used in hormone replacement therapy may reduce the risk of colorectal cancer in women.

Surgery to remove the tumor is the only way to cure the disease, and early detection is the best preparation for successful treatment. Depending on the stage of the cancer, surgery is generally followed with chemotherapy. If the tumor is particularly large, radiation may be necessary before or after surgery.

Certain medications and/or supplements may help prevent the development of polyps and/or colorectal cancer. Modifying lifestyle, particularly avoiding red meat, losing weight, quitting smoking, and increasing physical activity, may help prevent the disease—even in individuals with a family history of the condition. Omega-3 fatty acids and plant chemicals called lignans, found in flaxseed and olive oil, show particular promise for reducing the risk of colorectal cancer and preventing the spread of the disease.

An unhealthy lifestyle may increase the risk of colorectal cancer even in people who have no family history of the condition. Some experts believe that adjusting lifestyle habits may decrease the likelihood of developing colorectal cancer by as much as 70% in some individuals. In addition, even though family history significantly influences an individual's susceptibility to colorectal cancer, lifestyle factors appear to influence which susceptible individuals actually develop the disease.

A large, population-based study of men and women in Hawaii found that the following lifestyle factors were linked with colorectal cancer:

• Smoking
• Alcohol consumption
• History of diabetes
• Frequent constipation
• High-calorie diet
• Obesity
• Physical inactivity
• Low vegetable fiber intake (this association is controversial)
• High levels of insulin (hormone that controls blood sugar levels)
• Meat consumption

Findings from two very large studies of health professionals have recently supported the association between colorectal cancer and physical inactivity and obesity. Research continues to point to the idea that exercise and low-calorie diets can help to prevent colorectal cancer.

After surgery, chemotherapy (the use of anticancer drugs to destroy cancer cells) may be given to kill any cancerous cells that remain in the body. Chemotherapy controls the spread of the disease and improves survival rates over time. The following chemotherapeutic medications are used alone or in combination to treat colorectal cancer:

• Fluorouracil (5-FU)—often used in combination with leucovorin for 6 months after surgery; reduces the rate of recurrence and improves chances of survival; common side effects include nausea, diarrhea, inflammation of the skin and lining of the mouth, and lowered white blood cell count which increases the chance of developing an infection and anemia
• Leucovorin—a form of folic acid often used in combination with 5-FU; side effects are rare but can include rash, itching, and wheezing
• Levamisole—can be used in combination with 5-FU; potential side effects are numerous and include nausea, vomiting, diarrhea, loss of appetite, abdominal pain, lower extremity swelling, insomnia, fatigue, headache, hair loss, dizziness, muscle and joint paints, and depression

For colorectal cancer that has metastasized, or spread, doctors generally use 5-FU in combination with other drugs. One regimen approved by the United States Food and Drug Administration for metastatic colorectal cancer is 5-FU, leucovorin, and irinotecan. With the addition of irinotecan, the progression of the disease significantly slowed and survival improved compared to the 5-FU/leucovorin combination. However, an unexpectedly high death rate in two recent studies by the National Cancer Institute has brought the addition of irinotecan into question. There are also other medications currently under investigation for metastatic colon cancer.

Long-term use of aspirin, other nonsteroidal anti-inflammatory drugs (NSAIDs), and hormone replacement therapy have shown promise in the prevention and treatment of colorectal cancer.

• Aspirin—may reduce the risk of polyps and colorectal cancer by up to 44%; further studies are needed
• NSAIDs—reduced the number of polyps by 90% and colon tumors by 55% in animals; studies in humans are needed
• Hormone-replacement therapy (HRT)—over the past 20 years, the rate of death from colorectal cancer among women has decreased far more than the rate among men. Studies suggest that this may be due to the increasing use of hormone-replacement therapy by women after menopause.

Surgery is the treatment of choice for colorectal cancer because it is the only possible cure for the disease. The outlook is best when the disease is detected at an early stage. Before becoming cancerous, polyps can be removed during a colonoscopy. Depending on the severity and location of the cancer, including whether or where it has spread, an individual may need a partial or total removal of the colon (colectomy) and/or rectum (rectal resection). During surgery, the surgeon also examines other abdominal organs for signs of cancer. If cancer has spread to the liver, a portion of this organ may be removed as well. After removing the tumor and nearby tissue, the surgeon reconnects the healthy portions of the colon or rectum. If the healthy portions of the colon or rectum cannot be reconnected, a temporary or permanent opening (stoma) is made through the wall of the abdomen into the colon to provide a new path for waste material to leave the body. This procedure is called a colostomy. Radiation may also be used before or during surgery (called intraoperative radiotherapy) to shrink the tumor, and it may be recommended following surgery for certain stages of colorectal cancer to reduce the risk of recurrence. Following surgery, colonoscopies are performed every 3 to 6 months for 3 years to detect recurrence.

Meat and Animal Fat

Diets rich in red meat appear to be linked with increased risk of colorectal cancer. For example, Western countries with high rates of meat consumption, such as Australia and the United States, have particularly high rates of colorectal cancer. Although the reason for this association is not entirely clear, some researchers speculate that it may be related to overall intake of animal fat and protein. In a study of nearly 48,000 male health professionals in the United States, men who ate red meat five or more times per week were significantly more likely to develop colon cancer than men who consumed meat less than once a month. Interestingly, sources of animal fat and protein other than red meat—such as dairy products, fish, and poultry—were not associated with an increased risk for the condition. The researchers suggest that red meat, in particular, is detrimental to the colon. One theory scientists have offered is that the high amount of iron found in meat (and subsequently concentrated in the feces of those who eat meat) boosts levels of free radicals in the colon. Free radicals are substances that cause damage to cells and increase the risk of developing cancer. Another theory is that there are a lot of cancer-causing substances in meat. Further research is necessary to determine what element of red meat contributes to the development of colorectal cancer. Until more information becomes available, it is best for people with colorectal cancer to avoid eating red meat.

Polyunsaturated Fatty Acids

Some experts believe that omega-3 fatty acids may prove to be valuable in preventing colon cancer or treating it in its early stages, but not in later stages when the cancer has spread to other parts of the body. Studies in animals show that diets rich in omega-6 fatty acids may promote growth of colon tumors, whereas diets high in omega-3 fatty acids inhibit the growth of such tumors. Diets in certain Western countries, such as the United States, significantly favor omega-6 fatty acids over omega-3 fatty acids, at a ratio of about 20:1. The balance for optimum health and disease prevention is 2:1. The results of laboratory, animal, and population-based studies suggest that enriching the diet with omega-3 fatty acids may help protect against colorectal cancer specifically. For example, populations (such as the Eskimo) that consume diets rich in omega-3 fatty acids have a lower incidence of colorectal cancer. Similarly, patients with polyps and early signs of cancerous changes in the colon found that their abnormal cellular changes returned to normal after consuming omega-3 fatty acids in the form of EPA and DHA (both of which come from coldwater fish or fish oil capsules). However, results of an animal study suggest that once colorectal cancer has spread to other parts of the body, such as the liver, omega-3 fatty acids may lose their preventive effect. In this study of rats with late-stage colorectal cancer, omega-3 fatty acids actually promoted the growth of cancer cells in the liver. Until more information is available, it is best for people with late-stages of colorectal cancer to avoid omega-3 fatty acid supplements and diets rich in this substance.

Fiber

Studies reporting on the value of a high-fiber diet for colorectal cancer are somewhat conflicting. Although some population-based studies have found that fiber protects against colorectal cancer, most large clinical studies have shown a minimal association, at best, between fiber intake and decreased risk of colorectal cancer.

Lignans

Lignans are plant chemicals found in fruits, vegetables, and cereals, and in high concentrations in olive oil and flaxseed. Laboratory studies suggest that lignans slow growth of colon tumor cells, although the mechanism for this action is unclear.

Olive Oil

A review of studies from 28 countries and four continents suggests that higher olive oil intake is linked with decreased incidence of colorectal cancer. Olive oil appears to decrease the amount of deoxycyclic acid (a substance that promotes changes in the mucous membrane, polyp formation, and the progression of benign polyps to cancerous tumors) in the colon and rectum. In addition, olive oil is a monounsaturated fat that is low in omega-6 fatty acids, so it also improves the omega-6 to omega-3 ratio in the body. Extra virgin olive oil is rich in antioxidants, including flavonoids and lignans, which help prevent age-related damage to cells. Lignans in particular, but also other antioxidants in olive oil, may be protective against colorectal cancer.

Flaxseed

Flaxseed is the richest source of lignan precursors (substances that can be transformed into lignans) for mammals. Flaxseed and flaxseed oils significantly reduced the number of abnormal cell growths—early markers of colon cancer—in the colons of rats. Further studies are needed to determine whether flaxseed offers such protective effects against colorectal cancer in humans.

Calcium

Although some studies are conflicting, mounting evidence suggests that calcium may help protect against colorectal cancer. For example, population-based studies have found that people who consume high amounts of calcium, vitamin D, and milk in their diets are significantly less likely to develop colorectal cancer than those who consume low amounts of the same substances. Other studies have suggested that calcium and vitamin D supplements decrease the risk of colorectal cancer in both men and women. Although it is best to obtain calcium and vitamin D from the diet, the suggested amounts for the prevention and treatment of colorectal cancer (800 IU/day of vitamin D and 1800 mg/day of calcium) will most likely require supplementation.

Folate

Folate (vitamin B9), a nutrient found in both vegetables and fruit, appears to protect against the development of cancer. Although it is not clear how this works, some researchers speculate that folate keeps DNA (the genetic material in cells) healthy and prevents mutations that can lead to cancer. Population-based studies have found that colorectal cancer is less common among individuals with very high dietary intakes of folate. Conversely, low folate intake (particularly when accompanied by high alcohol intake) increases risk of benign colorectal tumors as well as cancer. To have a significant effect on reducing the risk of colorectal cancer, it appears that at least 400 mcg of folate per day for at least 15 years is required.

Antioxidants

According to the American Institute of Cancer Research, vegetables reduce the risk of colorectal cancer. In fact, diets rich in fruits and vegetables are believed to protect against a variety of cancers. Fruits and vegetables are rich in vitamins (such as folate) and antioxidants (such as vitamins A, C, E, lutein, and lycopene). Some convincing population-based studies have found that diets rich in lutein (found in spinach, broccoli, and lettuce) and lycopene (found in tomatoes) may lower the risk of developing colorectal cancer. More research would be helpful in determining how antioxidants reduce the risk of colorectal cancer as well as the precise amount of antioxidants necessary to lower the risk of developing the disease.

Selenium, another important antioxidant, may also help prevent colorectal cancer. Studies examining whether selenium protects against skin cancer have found that people who take the supplement are also significantly less likely to develop colorectal cancer than those who do not take the supplement.

Soy

Genistein, an isoflavone (plant pigment) derived from soy, has demonstrated anticancer effects in laboratory studies, including against colon cancer cells. However, animal studies to date have been conflicting, with some suggesting that genistein may boost tumor growth in the colon. Most medical experts agree that the evidence for the anticancer effects of soy is weak thus far, and that further research is necessary before conclusions can be drawn and decisions made regarding isoflavones and cancer.

Green Tea (Camellia sinensis)

The cancer-protective effects of green tea has been reported in several population-based and animal studies. Green tea contains chemicals called polyphenols that act as powerful antioxidants and have been shown to help prevent cancer. However, studies on the effects of green tea on colon or rectal cancer have produced conflicting results. Some studies show decreased risk in those who drink the tea, while others show increased risk. Further research is needed before green tea can be recommended for the prevention of colorectal cancer.

Preliminary studies also suggest that the following herbs may prove helpful in protecting against the development and spread of colorectal cancer:

• Gold thread (Coptis trifolia)
• Skullcap (Scutellaria lateriflora)
• Lemon grass (Cymbopogon citratus)
• Garlic (Allium sativum)
• Curcumin (Curcuma longa)

While acupuncture is not used as a treatment for cancer itself, evidence suggests it can be a valuable therapy for cancer-related symptoms (particularly nausea and vomiting that often accompanies chemotherapy treatment). There have also been studies indicating that acupuncture may help reduce pain and shortness of breath. Acupressure (pressing on rather than needling acupuncture points) has also proved useful in controlling breathlessness; this is a technique that patients can learn and then use to treat themselves.

Some acupuncturists prefer to work with a patient only after the completion of conventional medical cancer therapy. Others will provide acupuncture and/or herbal therapy during active chemotherapy or radiation. Acupuncturists treat cancer patients based on an individualized assessment of the excesses and deficiencies of qi located in various meridians. In many cases of cancer-related symptoms, a qi deficiency is usually detected in the spleen or kidney meridians.

Relaxation techniques are beneficial for individuals undergoing surgery. In one study it was observed that patients who received standard care plus relaxation techniques in the form of guided imagery audiotapes before, during, and after surgery experienced significantly better sleep and less pain following the surgery than patients who received only standard care.

Colorectal cancer may be detected late in pregnant women because symptoms of the disease, such as rectal bleeding, nausea, and vomiting, resemble the symptoms of pregnancy. Pregnant women should avoid chemotherapy and radiation therapy. Surgery puts the fetus at risk, therefore folic acid and nutritional needs are usually maintained during pregnancy and treatment is postponed until after the baby is delivered.

Follow-up care after treatment for colorectal cancer is very important. If the cancer returns or if new cancer develops, it should be treated as soon as possible. If left untreated, colorectal cancer can spread to the liver or lungs or a tumor may block the colon. In some cases, individuals with colorectal cancer may need to have their entire colon or rectum removed. If the surgeon cannot reconnect healthy portions of the colon or rectum, a temporary or permanent surgical opening (stoma) is made through the wall of the abdomen into the colon to provide a new path for waste material to leave the body. After this procedure, a special bag is worn to collect body waste. Individuals who wear the bag may need counseling on how to care for the stoma as well as how to deal with the emotional difficulties associated with this procedure.

The outlook in cases of colorectal cancer depends on how deeply the tumor has penetrated into the tissue and whether the cancer has spread to lymph nodes in the abdominal region or to other areas of the body. Following are the proportions of individuals who survive at least 5 years based on the stage of their disease when it was first diagnosed:

• Stage A—more than 90%
• Stages B1 and B2—85%
• Stage C—70% to 80%
• Stage D—5%

Albanes D, Malila N, Taylor PR, et al. Effects of supplemental a-tocopherol and b-carotene on colorectal cancer: results from a controlled trial (Finland). Cancer Causes Control. 2000;11:197-205.

Alberts DS, Martínez ME, Roe DJ, et al. Lack of effect of a high-fiber cereal supplement on the recurrence of colorectal adenomas. N Eng J Med. 2000;342(16):1156-1162.

Alimi D, Rubino C, Leandri EP, Brule SF. Analgesic effects of auricular acupuncture for cancer pain [letter]. J Pain Symptom Manage. 2000;19(2):81-82.

Anti M, Armelau F, Marra G, et al. Effects of different doses of fish oil on rectal cell proliferation in patients with sporadic colonic adenomas. Gastroenterology. 1994;107(6):1892-1894.

Baron JA, Beach M, Mandel JS, et al. Calcium supplements for the prevention of colorectal adenomas. N Eng J Med. 1999;340:101-107.

Biasco G, Zannoni U, Paganelli GM, et al. Folic acid supplementation and cell kinetics of rectal mucosa in patients with ulcerative colitis. Cancer Epidemiol Biomarkers Prev. 1997;6:469-471.

Bonithon-Kopp C, Kronborg O, Giacosa A, Rath U, Faivre J. Calcium and fibre supplementation in prevention of colorectal adenoma recurrence: a randomised intervention trial. European Cancer Prevention Organisation Study Group. Lancet. 2000;356:1300-1306.

Bushman JL. Green tea and cancer in humans: a review of the literature. Nutr Cancer. 1998;31(3):151-159.

Choi S-W, Mason JB. Folate and carcinogenesis: an integrated scheme. J Nutr. 2000:130:129-132.

Chute CG, Willett WC, Colditz GA, et al. A prospective study of body mass index, height, and smoking on risk of colorectal cancer in women. Cancer Causes Control. 1991;2(2):117-124.

Clark LC, Combs GF, Turnbull BW, et al. Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. JAMA. 1996;276:1957-1964.

Davies MJ, Bowey EA, Adlercreutz H, Rowland IR, Rumsby PC. Effects of soy or rye supplementation of high-fat diets on colon tumour development in azoxymethane treated rats. Carcinogenesis. 1999;20(6):927-931.

de Deckere EAM. Possible beneficial effect of fish and fish n-3 polyunsaturated fatty acids in breast and colorectal cancer. Euro J Cancer Prev. 1999;8:213-221.

Douillard JY, Cunningham D, Roth AD, Navarro M, James RD, Karasek P, et al. Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: a multicentre randomised trial. Lancet. 2000;355:1041-1047.

Ezzo J, Berman B, Hadhazy VA, Jadad AR, Lao L, Singh BB. Is acupuncture effective for the treatment of chronic pain? A systematic review. Pain. 2000;86:217-225.

Filshie J, Penn K, Ashley S, Davis CL. Acupuncture for the relief of cancer-related breathlessness. Palliat Med. 1998;10:145-150.

Finley JW, Davis CD, Feng Y. Selenium from high selenium broccoli protects rats from colon cancer. J Nutr. 2000;130:2384-2389.

Fleischauer AT, Poole C, Arab L. Garlic consumption and cancer prevention: meta-analyses of colorectal and stomach cancers. Am J Clin Nutr. 2000;72:1047-1052.

Flood A, Schatzkin A. Colorectal cancer: does it matter if you eat your fruits and vegetables? J Natl Cancer Inst. 2000;92(21):1706-1707.

Fukutake M, Yokota S, Kawamura H, et al. Inhibitory effect of Coptidis rhizoma and Scutellariae radix on azoxymethane-induced aberrant crypt foci formation in rat colon. Biol Pharm Bull. 1998;21(8):814-817.

Garland CF, Garland FC, Gorham ED. Calcium and vitamin D: their potential roles in colon and breast cancer prevention. Ann NY Acad Sci. 1999;889:107-119.

Giacosa A, Frascio F, Sukkar SG, Roncella S. Food intake and body composition in cancer cachexia. Nutrition. 1996;12:S20-S23.

Giardiello FM, Offerhause GJ, DuBois RN. The role of nonsteroidal anti-inflammatory drugs in colorectal cancer prevention. Eur J Cancer. 1995;31A(7-8):1071-1076.

Giovannucci E, Stampfer MJ, Colditz GA, et al. Multivitamin use, folate, and colon cancer in women in the Nurses' Health Study. Ann Intern Med. 1998;129:517-524. Accessed at www.acponline.org/journals/annals/01oct98/folate.htm on May 21, 2001.

Giovannucci E, Colditsz GA, Stampfer MJ, Willett WC. Physical activity, obesity, and risk of colorectal adenoma in women (United States). Cancer Causes Control. 1996;7:253-263.

Giovannucci E, Ascherio A, Rimm EB, Colditz GA, Stampfer MJ, Willett WC. Physical activity, obesity, and risk of colorectal adenoma in men. Ann Intern Med. 1995a;122:327-334. Accessed at www.acponline.org/journals/annals/01mar95/physact.htm on May 21, 2001.

Giovannucci E, Egan KM, Hunter DJ, et al. Aspirin and the risk of colorectal cancer in women. N Engl J Med 1995b;333(10):609-614.

Giovannucci E, Rimm EB, Stampfer MJ, et al. Aspirin use and the risk for colorectal cancer and adenoma in male health professionals. Ann Intern Med. 1994a;121(4):241-246.

Giovannucci E, Rimm EB, Stampfer MJ, Colditz GA, Ascherio A, Willett WC. Intake of fat, meat, and fiber in relation to risk of colon cancer in men. Cancer Res. 1994b;54:2390-2397.

Greenberg ER, Baron JA, Tosteson TD, et al. A clinical trial of antioxidant vitamins to prevent colorectal adenoma. N Engl J Med. 1994;331:141-147.

Griffini P, Fehres O, Klieverik L, et al. Dietary W-3 polyunsaturated fatty acids promote colon carcinoma metastasis in rat liver. Cancer Res. 1998;58:3312-3319.

Helms JR, Gallaher DD. The effect of dietary soy protein isolate and genistein on the development of preneoplastic lesions (aberrent crypts) in rats. J Nutr. 1995;125:802S.

Holt PR. Dairy foods and prevention of colon cancer: human studies. J Am Coll Nutr. 1999;18(suppl 5):379S-391S.

Jänne PA, Mayer RJ. Chemoprevention of colorectal cancer. N Engl J Med. 2000;342(26):1960-1968. 

Jenab M, Thompson LU. The influence of flaxseed and lignans on colon carcinogenesis and b-glucuronidase activity. Carcinogenesis. 1996;17(6):1343-1348.

Ji B-T, Chow W-H, Hsing AW, et al. Green tea consumption and the risk of pancreatic and colorectal cancers. Int J Cancer. 1997;70:255-258.

Kampman E, Slattery ML, Caan B, Potter JD. Calcium, vitamin D, sunshine exposure, dairy products and colon cancer risk (United States). Cancer Causes Control. 2000:11:459-466.

Kawamori T, Lubet R, Steele VE, et al. Chemopreventive effect of curcumin, a naturally occurring anti-inflammatory agent, during the promotion/progression stages of colon cancer. Cancer Res. 1999;59:597-601.

La Vecchia C, Braga C, Negri E, et al. Intake of selected micronutrients and risk of colorectal cancer. Int J Cancer. 1997;73:525-530.

Le Marchand L, Wilkens LR, Hankin JH, Kolonel LN, Lyu LC. Independent and joint effects of family history and lifestyle on colorectal cancer risk: Implications for prevention. Cancer Epidemiol Biomarkers Prevent.1999;8:45-51.

Le Marchand L, Hankin JH, Wilkens LR, Kolonel LN, Englyst HN, Lyu L. Dietary fiber and colorectal cancer risk. Epidemiology. 1997a;8:658-665.

Le Marchand L, Wilkens LR, Kolonel LN, Hankin JH, Lyu LC. Associations of sedentary lifestyle, obesity, smoking, alcohol use, and diabetes with the risk of colorectal cancer. Cancer Res.1997b;57:4787-4794.

Maa SH, Gauthier D, Turner M. Acupressure as an adjunct to a pulmonary rehabilitation program. J Cardiopulm Rehabil. 1997;17(4):268-276.

Mayer RJ. Gastrointestinal tract cancer. In: Fauci AS, Braunwald E, Isselbacher KJ, et al, eds. Harrison's Principles of Internal Medicine. 14th ed. New York, NY: McGraw-Hill; 1998:571-576.

Messina M, Bennink M. Soy foods, isoflavones and risk of colonic cancer: A review of the in vitro and in vivo data. Bailliéres Clin Endocrinol Metab. 1998:12(4):707-728.

Michels KB, Giovannucci E, Joshipura KJ, et al. Prospective study of fruit and vegetable consumption and incidence of colon and rectal cancers. J Natl Cancer Inst. 2000;92:1740-1752.

Narisawa T, Fukaura Y, Hasebe M, et al. Prevention of N-methylnitrosourea-induced colon carcinogenesis in F344 rats by lycopene and tomato juice rich in lycopene. Jpn J Cancer Res. 1998;89:1003-1008.

NIH Consensus Statement: Acupuncture. National Institutes of Health, Office of the Director. 1997;15(5):1-34. Accessed at http://odp.od.nih.gov/consensus/cons/107/107_statement.htm on September 24, 2001.

Owen RW, Giacosa A, Hull WE, Haubner R, Spiegelhalder B, Bartsch H. The antioxidant/anticancer potential of phenolic compounds isolated from olive oil. Eur J Cancer. 2000a;36(10):1235-1247.

Owen RW, Mier W, Giacosa A, Hull WE, Spiegelhalder B, Bartsch H. Identification of lignans as major components in the phenolic fraction of olive oil. Clin Chem. 2000b;46(7):976-988.

Pan CX, Morrison RS, Ness J, Fugh-Berman A, Leipzig RM. Complementary and alternative medicine in the management of pain, dyspnea, and nausea and vomiting near the end of life: a systematic review. J Pain Symptom Manage. 2000;20(5):374-387.

Piazza GA, Alberts DS, Hixson LJ, et al. Sulindac sulfone inhibits azoxymethane-induced colon carcinogenesis in rats without reducing prostaglandin levels. Cancer Res. 1997;57(14):2909-2915.

Pietinen P, Malila N, Virtanen M, et al. Diet and risk of colorectal cancer in a cohort of Finnish men. Cancer Causes Control. 1999;10:387-396.

Potter JD. Nutrition and colorectal cancer. Cancer Causes Control. 1996;7:127-146.

Psathakis D, Wedemeyer N, Oevermann E, Krug F, Siegers CP, Bruch HP. Blood selenium and glutathione peroxidase status in patients with colorectal cancer. Dis Colon Rectum. 1998;41:328-335.

Rao CV, Wang CX, Simi B, et al. Enhancement of experimental/colon cancer by genistein. Cancer Res. 1997;57:3717-3722.

Rao CV, Rivenson A, Simi B, et al. Chemoprevention of colon carcinogenesis by sulindac, a nonsteroidal anti-inflammatory agent. Cancer Res. 1995;55(7):1464-1472.

Renzi C, Peticca L, Pescatori M. The use of relaxation techniques in the perioperative management of proctological patients: preliminary results. Int J Colorectal Dis. 2000;15(5-6):313-316.

Russo MW, Murray SC, Wurzelmann JI, Woosley JT, Sandler RS. Plasma selenium levels and the risk of colorectal adenomas. Nutr Cancer. 1997;28(2):125-129.

Sargent DJ, Niedzwiecki D, O'Connell MJ, Schilsky RL. N Engl J Med. To be published June 21, 2001.

Schatzkin A, Lanza E, Corle D, et al. Lack of effect of a low-fat, high-fiber diet on the recurrence of colorectal adenomas. NEJM. 2000;342(16):1149-1155.

Sellick SM, Zaza C. Critical review of five nonpharmacologic strategies for managing cancer pain. Cancer Prev Control. 1998;2(1):7-14.

Sharma RA, Ireson CR, Verschoyle RD. Effects of dietary curcumin on glutathione S-Transferase and Malondialdehyde-DNA adducts in rat liver and colon mucosa: relationship with drug levels. Clin Cancer Res. 2001;7:1452-1458.

Shen J, Wenger N, Glaspy J, et al. Electroacupuncture for control of myeloablative chemotherapy-induced emesis. JAMA. 2000;284(21):2755-2761.

Simopoulos AP. Essential fatty acids in health and chronic disease. Am J Clin Nutr. 1999;70(3 suppl):560S-569S.

Slattery ML, Benson J, Curtin K, Ma K-N, Schaeffer D, Potter JD. Carotenoids and colon cancer. Am J Clin Nutr. 2000;71:575-582.

Slattery ML, Edwards S, Anderson K, Caan B. Vitamin E and colon cancer: is there an association? Nutr Cancer. 1998:30(3):201-206.

Stoneham M, Goldacre M, Seagroatt V, Gill L. Olive oil, diet and colorectal cancer: an ecological study and a hypothesis. J Epidemiol Community Health. 2000;54:756-760.

Suaeyun R, Kinouchi T, Arimochi H, Arimochi H, Vinitketkumnuen U, Ohnishi Y. Inhibitory effects of lemon grass (Cymbopogon citratus Stapf) on formation of azoxymethane-induced DNA adducts and aberrant crypt foci in the rat colon. Carcinogenesis. 1997;18(5):949-955.

Sung MK, Lautens M, Thompson LU. Mammalian lignans inhibit the growth of estrogen-independent human colon tumor cells. Anticancer Res. 1998;18(3A):1405-1408.

Thiagarajan D, Bennink MR, Bourquin LD, Kavas FA. Prevention of precancerous colonic lesions in rats by soy flakes, soy flour, genistein, and calcium. Am J Clin Nutr. 1998;68(suppl):1394S-1399S.

Thun MJ, Namboordiri MM, Heath CW Jr. Aspirin use and reduced risk of fatal colon cancer. N Engl J Med. 1991;325(23):1593-1596.

Tsai W-S, Nagawa H, Kaizaki S, Tsuruo T, Muto T. Inhibitory effects of n-3 polyunsaturated fatty acids on sigmoid colon cancer transformants. J Gastroenterol. 1998;33:206-212.

Turowski GA, Rashid Z, Hong F, Madri J, Basson MD. Glutamine modulates phenotype and stimulates proliferation in human colon cancer cell lines. Cancer Res. 1994;54:5974-5980.

Vickers AJ. Can acupuncture have specific effects on health? A systematic review of acupuncture antiemesis trials. J R Soc Med. 1996;89:303-311.

Wigmore SJ, Barber MD, Ross JA, Tisdale MJ, Fearon KC. Effect of oral eicosapentaenoic acid on weight loss in patients with pancreatic cancer. Nutr Cancer. 2000;36(2):177-184.