Colon cancer

Colon cancer

1.      Introduction:

Cancer begins in cells, the building blocks that make up tissues. Tissues make up the organs of the body. Normally, cells grow and divide to form new cells as the body needs them. When cells grow old, they die, and new cells take their place. Sometimes this orderly process goes wrong. New cells form when the body does not need them, and cells do not die when they should. These extra cells can form a mass of tissue called a growth or tumor. Tumors can be benign or malignant:

• Benign tumors are not cancer:

– Benign tumors are rarely life-threatening.

– Generally, benign tumors can be removed, and they usually do not grow back.

– Cells from benign tumors do not invade the tissues around them.

– Cells from benign tumors do not spread to other parts of the body.

• Malignant tumors are cancer:

– Malignant tumors are generally more serious than benign tumors. They may be life-threatening.

– Malignant tumors usually can be removed, but sometimes they grow back.

Cancer of the colon or rectum is also called colorectal cancer. In the United States, colorectal cancer is the fourth most common cancer in men, after skin, prostate, and lung cancer. It is also the fourth most common cancer in women, after skin, lung, and breast cancer. Colorectal carcinoma remains the second leading cause of death from malignancy 1 .

2. The particular disease process

Colon cancer is a cancer that is developed in the large intestine (colon), the lower part of your digestive system 2 .It begins as a no cancerous polyp that ranges in size from a few millimeters to several centimeters in diameter and they may be single or multiple 3 ,which may eventually change into cancer. This polyp is a growth of tissue that develops on the lining of the colon .there is certain kinds of adenomas are most likely to become cancers. Once cancer forms in large intestine, it eventually can begin to grow through the lining and into the wall of the colon. Cancers that have invaded the wall can grow into blood and lymph vessels. 

Cancer cells first drain into nearby lymph nodes and starts traveling to distant parts of the body in a process called "Metastasis". The extent to which a Colon cancer has spread is described as its stage. Cancers that have not yet begun to invade the wall of the colon are called "Carcinomas in situ"and are not counted in cancer statistics4.

Colon cancer stages may be described as follows:

Local: cancers that have grown into the wall of the colon, but have not extended through the wall to invade nearby tissues.

Regional: cancers that have spread through the wall of the colon and have invaded nearby tissue, or that have spread to nearby lymph nodes.

      Distant: Cancers that have spread to other parts of the body, such as the liver and lung 5

3. The symptoms and signs

Early colorectal cancer often has no symptoms, but over time some polyps in the wall of the colon grow and become malignant  6.Symptoms usually do not develop until there is a full blown development of polyposis 7  and as they grow, they can bleed or obstruct the intestine, and there may be any of these warning signs:

A change in bowel habits, Diarrhea, constipation, or feeling that the bowel does not empty completely, Blood in the stool, Stools that are narrower than usual, General abdominal discomfort (frequent gas pains, bloating, fullness, and/or cramps), Weight loss with no known reason, Constant tiredness, Nausea and vomiting 8. 

Another sign that may be useful for the doctors if asking the patient about the bleeding they may have, that Dark-red blood or blood mixed with the stool is more likely to be associated with colorectal cancer , especially when associated with change in bowel habit and/or abdominal pain9 . Most often, these symptoms are not due to cancer. Other health problems can cause the same symptoms. Anyone with these symptoms should see a doctor so that any problem can be diagnosed and treated as early as possible. Usually, early cancer does not cause pain. It is important not to wait to feel pain before seeing a doctor10. If the symptoms of colon cancer are detected early enough, colon caner maybe preventable.

4. Using screening methods to detect colon cancer

Using screening techniques in this disease, identifies individuals who are more likely to have colorectal carcinoma or adenomatous polyps from among those without signs or symptoms of disease and helps in early detection of this kind of cancer 11 .The goal of screening for colon cancer is the detection of early-stage adenocarcinomasto12 and reduce mortality from the disease. It is important to note that once the screening results are positive, a complete investigation of the entire colon and  is mandated, preferably by CT colonography, total colonoscopy, or with flexible sigmoidoscopy and barium enema, to identify suspicious polyps or carcinomas13 .This disease may be investigated by:

Fecal occult blood test (FOBT): Cancerous tumors and some large polyps bleed intermittently into the intestine. The FOBT can detect very small quantities of blood in stool.
Flexible sigmoidoscopy: A slender, hollow lighted tube inserted through the rectum into the colon to view the inside of it. This test is followed by colonoscopy if a polyp tumor is found. Both of the previous tests may be used both to improve early detection of colon cancers.

Colonscopy: just like the Sigmoidoscopy, but it is much longer and uses more complex instrument, which allows doctors to view the entire colon and remove polyps if present.

·         Barium enema with air contrast or Double-contrast Barium enema: allows complete radiological examination of the colon using X-rays. If there are any kind of polyps, a colonoscopy is recommended to the patient14.

Blood count and routine biochemistry
·           Ultrasound,CT and MRI may help evaluate tumor size and local and secondary spread, including hepatic metastases 15

         There are a couple emerging screening tests that are not yet ready for mass screening but have promising potential. One of those is "Computed tomography colonography (CTC)", which is not yet ready for a mass screening tests for colon cancers. It is used as a backup for an incomplete colonoscopy, or for patients who are not suitable for a colonoscopy. However, the advances in technology, techniques, and clinical studies have progressed rapidly. It will be just a matter of time that CTC will become another option for colon cancer screening .

Another new technique is "Fecal DNA testing", which is based on the idea that, because carcinoma is a disease of mutations that occur as tissue evolves from normal to adenoma to carcinoma, those mutations should be detectable in stool. Preliminary reports that persons with advanced carcinoma have detectable DNA mutations in stool .Such stool-based testing is appealing because it is noninvasive, requires no special colonic preparation, and has the capability of detecting neoplasia throughout the entire length of the colon .Future of such an approach would seem promising if sensitivity could be increased by additional markers such as methylation and if cost could be reduced16.

5. Different etiology of colon cancers

There are a number of factors that may be considered important in colon cancers causation, such as; Polyp-cancer sequence, because there are evidence that has accumulated to suggest that most, if not all, carcinomas develop from a precursor polyp. Also inflammatory bowel disease like Crohn’s disease17

Most colorectal cancers develop as a result of a stepwise progression from normal mucosa to adenoma to invasive cancer. This progression is controlled by the accumulation of alterations or mutations in a number of critical growth-regulating genes. These mutations occur in the genes.APC (adenomatous polyposis coli), K-ras, DCC, p53, hMSH2, and hMLH118. 

The alterations that occur in these genes can arise as a result of exposure to carcinogens (e.g. chemicals, dietary, viral or irradiation), spontaneous sporadic mutation, or an inherited gene defect. There is also some evidence that environmental factors such as diet may affect certain gene mechanisms. The changes may also arise on the background of chronic diseases such as ulcerative colitis19. 

Any change of those genes, may alter their products to such an extent that the function of a particular protein may be altered or lost. Protein plays an important role in the regulation of cell structure or growth and then, the cell will become abnormal. If the cell obtains a growth advantage it may become malignant20. Specific environmental factors are known to modify colorectal carcinoma (like shown in following figure)21. Bad habits of diet, smoking and alcohol drinking, may provide many reasons for being diagnosed with Colon cancer for many people22

From previous discussion, the risk factors for colorectal cancer23 are:

• Age: Colorectal cancer is more likely to occur as people get older. More than 90 percent of people with this disease are diagnosed after age 50. The average age at diagnosis is in the mid-60s.

• Colorectal polyps: Polyps are growths on the inner wall of the colon or rectum. They are common in people over age 50. Most polyps are benign (noncancerous), but some polyps (adenomas) can become cancer. Finding and removing polyps may reduce the risk of colorectal cancer.

· Family history of colorectal cancer: Close relatives (parents, brothers, sisters, or children) of a person with a history of colorectal cancer are somewhat more likely to develop this disease themselves, especially if the relative had the cancer at a young age. If many close relatives have a history of colorectal cancer, the risk is even greater24.

· Genetic alterations: Changes in certain genes increase the risk of colorectal cancer.

– Hereditary nonpolyposis colon cancer (HNPCC) is the most common type of inherited (genetic) colorectal cancer. It accounts for about 2 percent of all colorectal cancer cases. It is caused by changes in an HNPCC gene. About 3 out of 4people with an altered HNPCC gene develop colon cancer, and the average age at diagnosis of colon cancer is 44 25.

– Familial adenomatous polyposis (FAP) is a rare, inherited condition in which hundreds of polyps

form in the colon and rectum. It is caused by a change in a specific gene called APC. Unless familial adenomatous polyposis is treated, it usually leads to colorectal cancer by age 40. FAP accounts for less than 1 percent of all colorectal cancer cases. Family members of people who have HNPCC or FAP can have genetic testing to check for specific genetic changes. For those who have changes in their genes, health care providers may suggest ways to try to reduce the risk of colorectal cancer, or to improve

The detection of this disease. For adults with FAP, the doctor may recommend an operation to remove all

or part of the colon and rectum 26.

• Personal history of colorectal cancer: A person who has already had colorectal cancer may develop colorectal cancer a second time. Also, women with a history of cancer of the ovary, uterus (endometrium), or breast are at a somewhat higher risk of developing colorectal cancer.

• Diet: Studies suggest that diets high in fat (especially animal fat) and low in calcium, folate, and fiber may increase the risk of colorectal cancer. Also, some studies suggest that people who eat a diet very low in fruits and vegetables may have a higher risk of colorectal cancer. More research is needed to better understand how diet affects the risk of colorectal cancer.

• Cigarette smoking: A person who smokes cigarettes may be at increased risk of developing polyps and colorectal cancer. People who think they may be at risk should discuss this concern with their doctor. The doctor may be able to suggest ways to reduce the risk and can plan an appropriate schedule for checkups27.

6. Disease complications

1) Obstruction: Carcinoma is the most common cause of large bowel obstruction the patient often has had progressive difficulty in moving his or her bowels and has taken increasing doses of laxatives until the abdomen has become more distended with pain and eventual obstipation. Nausea and vomiting may supervene. Alternatively, the patient may present with sudden, severe, colicky abdominal pain that persists, and investigation may reveal a complete obstruction28.

2) Perforation:

The incidence of perforation associated with carcinoma of the colon may result in peritonitis, abscess formation, adherence to a neighboring structure or fistulous communication into a viscus.If acute obstruction supervenes in the middle or distal colon, the cecum may perforate. However, the most common form of perforation is associated with the carcinoma itself. Patients without obstruction but with perforation of the carcinoma are also gravely ill and require immediate laparotomy after some correction of dehydration and electrolyte depletion. Patients without obstruction but with perforation of a carcinoma may present with a localized peritonitis29.

3) Bleeding:

Bleeding is a common symptom of colorectal carcinoma, but massive bleeding is an uncommon presentation.

4) Unusual infections associated with colorectal carcinoma may, in some instances, be the sole clue to the presence of a malignancy. The infections are either related to invasion of tissues or organs in close proximity to the neoplasm or secondary to distant seeding by transient bacteremia arising from necrotic carcinomas. Included endocarditic (Streptococcus bovis bacteremia), meningitis (S.bovis bacteremia), nontraumatic gas gangrene (Escherichia coli), emphysema (E. coli, Bacteroides fragilis), hepatic abscesses (Clostridium septicum), retroperitoneal abscesses (E. coli, B. fragilis), clostridial sepsis, and colovesical fistulas with urosepsis (E. coli). Other infections associated with colon carcinoma, including nontraumatic crepitant cellulitis, suppurative thyroiditis, pericarditis, appendicitis, pulmonary microabscesses, septic arthritis, and fever of unknown origin   30.

7. Treatment of colon cancer

For colorectal cancer with lymph node metastasis, adjuvant chemotherapy is the recommended treatment31. The use of adjuvant chemotherapy is attractive because it may offer the possibility of identifying patients who are likely to have occult, residual, or disseminated disease at the time of operation. Chemotherapy is most effective when the burden of carcinoma is smallest and the fraction of malignant cells in growth phase is the highest. Many chemotherapeutic agents have been used singly or in combination in an effort to improve survival rates. A large number of studies have directed enormous energy to the subject of intravenous or oral administration of chemotherapeutic agents beginning 4 to 6 weeks after operation. For the most part, none of the early studies directly indicated that adjuvant chemotherapy was of overall benefit to the survival of patients with colon carcinoma32. The management of colorectal cancer usually involves one of more of the following treatment modalities:

7.1 surgery

Surgery is the most common treatment for colorectal cancer. It is a type of local therapy. It treats the cancer in the colon or rectum and the area close to the tumor. A small malignant polyp may be removed from the colon or upper rectum with a colonoscopy. Some small tumors in the lower rectum can be removed through the anus without a colonoscope. For a larger cancer, the surgeon makes an incision into the abdomen to remove the tumor and part of the healthy colon or rectum. Some nearby lymph nodes also may be removed. The surgeon checks the rest of the intestine and the liver to see if the cancer has spread33. When a section of the colon or rectum is removed, the surgeon can usually reconnect the healthy parts. 

However, sometimes reconnection is not possible. In this case, the surgeon creates a new path for waste to leave the body. The surgeon makes an opening (astoma) in the wall of the abdomen, connects the upper end of the intestine to the stoma, and closes the other end. The operation to create the stoma is called a colostomy. A flat bag fits over the stoma to collect waste, and a special adhesive holds it in place. For most people who have a colostomy, it is temporary. It is needed only until the colon or rectum heals from surgery. After healing takes place, the surgeon reconnects the parts of the intestine and closes the stoma. Some people, especially those with a tumor in the lower rectum, need a permanent colostomy34.

7.2Radiotherapy

Radiotherapy is the use of ionizing radiation in the treatment of primarily malignant disease exerting local control over tumour tissue. Ionizing radiation destroys cells in the body by physical, chemical and biological methods. Radiation cannot distinguish between cancer and normal cells, so all cells within the treatment field are damaged, although cancer cells cannot repair radiation damage as effectively as normal cells. The aim of treatment is to deliver the required dose of radiation to the target area while minimizing the dose to the surrounding normal tissue. This is achieved by careful treatment planning to produce the best possible outcome in terms of survival, symptom relief and side effects. The treatment area must be accurately imaged so that the radiation beam can be accurately targeted35.

7.3 chemotherapy

Chemotherapy uses drugs to destroy cancer cells. Chemotherapy can be used to destroy cancer cells after surgery, to control tumor growth or to relieve symptoms of colon cancer. Your doctor may recommend chemotherapy if your cancer has spread beyond the wall of the colon. In some cases, chemotherapy is used along with radiation therapy. Possible side effects of chemotherapy include nausea and vomiting, mouth sores, fatigue, hair loss and diarrhea36. Adjuvant chemotherapy after potentially curative surgery for colon cancer and radiotherapy for rectal cancer reduce the incidence of recurrence and improve survival. In patients with advanced colorectal cancer, palliative chemotherapy improves the quality of life and increases survival37.

7.4 Targeted drug therapy

Three drugs that target specific defects that allow cancer cells to proliferate are available to people with advanced colon cancer. The drugs bevacizumab (Avastin), cetuximab (Erbitux) and panitumumab (Vectibix) can be administered along with chemotherapy drugs or alone. Bevacizumab works to prevent tumors from developing blood vessels, which can deliver the oxygen and nutrients cancers need to survive. Cetuximab and panitumumab target a chemical signal that tells cells to divide and reproduce. Cetuximab and panitumumab can't cure colon cancer and currently remain experimental38.

7.5External beam radiotherapy

This is the most commonly used method of radiation treatment. The radiation beam is administered on to and into the patient from a source external to the patient’s body. Treatment is delivered by high-energy X-ray machines known as linear accelerators. A course of treatment is prescribed, which can be anything from a single session to treatment lasting up to six weeks, depending on the site and stage performance status of the individual; it lasts about 2–3 minutes a day. The X-ray beam is accurately targeted by markings on the individual’s skin or by the use of individually prepared Perspex shells 39.

7.6Brachytherapy

Otherwise known as sealed source therapy, Brach therapy is a radioactive source placed within a body cavity or tissue or supported close to the skin surface. It was developed from the use of radium, but has largely been replaced by other radioisotopes, the properties of which make them less of a potential radiation hazard; it allows the radioactive sources to be remotely after-loaded into the tumour site, thus reducing the radiation hazard to individuals. Liquid radioactive sources Also known as unsealed source therapy, this is a radioactive substance delivered via injection or taken orally, the most common being radioactive iodine in the treatment of thyroid cancer 40.

8. Side effect of colon cancer treatment

Because treatment often damages healthy cells and tissues, unwanted side effects are common. Side effects depend mainly on the type and extent of the treatment. Side effects may not be the same for each person, and they may change from one treatment session to the next41.

Surgery

It takes time to heal after surgery, and the time needed to recover is different for each person. Patients are often uncomfortable during the first few days. However, medicine can usually control their pain. Before surgery, patients should discuss the plan for pain relief with the doctor or nurse. After surgery, the doctor can adjust the plan if more pain relief is needed. It is common to feel tired or weak for a while. Also, surgery sometimes causes constipation or diarrhea. The health care team monitors the patient for signs of bleeding, infection, or other problems requiring immediate treatment. People who have a colostomy may have irritation of the skin around the stoma. The doctor, nurse, or enterostomal therapist can teach patients how to clean the area and prevent irritation and infection42.

Chemotherapy

The side effects of chemotherapy depend mainly on the specific drugs and the dose. In general, anticancer drugs affect cells that divide rapidly, and cause infections, bruise or patient to bleed easily. Chemotherapy can cause hair loss. Chemotherapy can cause poor appetite, nausea and vomiting, diarrhea, or mouth and lip sores. Many of these side effects can be controlled with drugs 43.

Radiation Therapy

The side effects of radiation therapy depend mainly on the amount of radiation given and the part of the body that is treated. Radiation therapy to the abdomen and pelvis may cause nausea, vomiting, diarrhea, bloody stools, rectal leakage, or urinary discomfort. In addition, the skin in the treated area may become red, dry, and tender. Patients are likely to become very tired during radiation therapy, especially in the later weeks of treatment. Resting is important, but doctors usually advise patients to try to stay as active as they can44.

9. Research on colon cancers

Doctors all over the country are conducting many types of clinical trials (research studies in which people volunteer to take part). Doctors are studying new ways to prevent, detect, diagnose, and treat colorectal cancer. Clinical trials are designed to answer important questions and to find out whether the new approach is safe and effective. Research already has led to advances in these areas, and researchers continue to search for more effective approaches. People who join clinical trials may be among the first to benefit if a new approach is shown to be effective. And if participants do not benefit directly, they still make an important contribution to medicine by helping doctors learn more about the disease and how to control it. Although clinical trials may pose some risks, researchers do all they can to protect their patients 45.

Research on Prevention

Recent studies suggest that certain drugs may help prevent colorectal cancer. Researchers are studying aspirin, celecoxib, and other drugs in people with a higher-than-average chance of developing this disease.

Research on Screening and Diagnosis

Researchers are testing new ways to check for polyps and colorectal cancer. One study is looking at the usefulness of virtual colonoscopy. This is a CT scan of the colon. Another study is using genetic testing to check stool samples for colorectal cancer cells 46.

Research on Treatment

Researchers are studying chemotherapy, biological therapy, and combinations of treatment:

• Chemotherapy: Researchers are testing new anticancer drugs and drug combinations. They also are studying combinations of drugs and radiation therapy before and after surgery.

• Biological therapy: New biological approaches also are under study. Biological therapy uses the body’s natural ability (immune system) to fight cancer. For example, researchers are studying treatment with monoclonal antibodies after surgery or with chemotherapy. A monoclonal antibody is a substance made in the laboratory that can bind to cancer cells. It can help kill cancer cells47.

10. Nutrition of colon cancer patients

It is important to eat well during cancer treatment.Eating well means getting enough calories to maintain a good weight and enough protein to keep up strength. Good nutrition often helps people with cancer feel better and have more energy. But eating well can be difficult. Patients may not feel like eating if they are uncomfortable or tired. Also, the side effects of treatment, such as poor appetite, nausea, vomiting, or mouth sores, can be a problem. Some people find that foods do not taste as good during cancer therapy. The doctor, dietitian, or other health care provider can suggest ways to maintain a healthy diet. 48.

11. Similarity between Colon cancer and other diseases

About one-third of all Crohn's disease cases involve only the small bowel, especially the ileum. About half of all cases involve the small bowel and colon, and about 20 percent of all cases affect the colon alone. Colon cancers only affect the colon. Some symptoms are similar between the two diseases. The first symptoms of Crohn's disease are often abdominal pain and diarrhea. Pain is felt in the area of the navel or on the right side. Joint pain, lack of appetite, weight loss, fatigue and fever are common 49.

 A link has been shown to exist between Crohn’s Disease and an increased chance of developing cancer; however, this risk is greatly increased if you have had IBD for an extensive period of time, such as 8-10 years, and it affects the entirety of your colon. If, on the other hand, only a small part of your colon is involved and you have not had the disease for a long period of time, you are less likely to develop cancer. Likewise, if Crohn’s does affects other areas of your digestive tract and not your colon, you are at less risk. Unfortunately, inactive Crohn’s Disease is just as likely to develop colon cancer as the active disorder. Therefore, the original onset of symptoms matters more than the frequency or intensity of flare-ups.It is sometimes difficult to detect colon cancer in Crohn’s sufferers as the early symptoms often mimic those of IBD. Diarrhea and rectal bleeding are common among Crohn’s patients and may not cause concern. .

As an extra precautionary measure, you should see your gastroenterologist at least once a year if you have had Crohn’s for more than 8 years. It may be necessary to have regular colonoscopies to identify any possible problems early. During a colonoscopy, your gastroenterologist may identify concerns from the appearance of your colon, as well as take biopsies to further examine possibly affected tissue. Unfortunately, a colonoscopy is not guaranteed to detect cancer if it is present; however a colonoscopy with multiple biopsies is the most reliable means currently available 50.

13. Rehabilitation

Rehabilitation is an important part of cancer care. The health care team makes every effort to help the patient return to normal activities as soon as possible. A person with a stoma needs to learn to care for it. Doctors, nurses, and enterostomal therapists can help. Often, enterostomal therapists visit the person before surgery to discuss what to expect. They teach the person how to care for the stoma after surgery. They talk about lifestyle issues, including emotional, physical, and sexual concerns. Often they can provide information about resources and support groups 51.

14. Follow-up Care

Follow-up care after treatment for colorectal cancer is important. Even when the cancer seems to have been completely removed or destroyed, the disease sometimes returns because undetected cancer cells remained somewhere in the body after treatment. The doctor monitors the person’s recovery and checks for recurrence of the cancer. Checkups help ensure that any changes in health are noted. Checkups may include a physical exam (including a digital rectal exam), lab tests (including fecal occult blood test and CEA test), colonoscopy, x-rays, CT scans, or other tests. Between scheduled visits with the doctor, patients should contact the doctor as soon as any health problems appear 52.

15. Support for People with Colorectal Cancer

Living with a serious disease such as colorectal cancer is not easy. People may worry about caring for their families, keeping their jobs, or continuing daily activities. Concerns about treatments and managing side effects, hospital stays, and medical bills are also common. Doctors, nurses, and other members of the health care team can answer questions about treatment, working, or other activities. Meeting with a social worker, counselor, or member of the clergy can be helpful to those who want to talk about their feelings or discuss their concerns. Often, a social worker can suggest resources for financial aid, transportation, home care, or emotional support. Support groups also can help. In these groups, patients or their family members meet with other patients or their families to share what they have learned about coping with the disease and the effects of treatment. Groups may offer support in person, over the telephone, or on the Internet. Patients may want to talk with a member of their health care team about finding a support group53.

12. Conclusion

Fighting Colon Cancer is not hard. You can take steps to reduce your risk of colon cancer by making changes in your everyday life. Take steps to:

Eat plenty of fruits, vegetables and whole grains. Fruits, vegetables and whole grains contain vitamins, minerals, fiber and antioxidants, which may play a role in cancer prevention. Try to eat five or more servings of fruits and vegetables every day, and to include a variety of produce in your diet.

Limit fat, especially saturated fat. Eat a low-fat diet. Avoid saturated fats from animal sources such as red meat. Other foods that contain saturated fat include milk, cheese, ice cream, and coconut and palm oils.

Eat a varied diet to increase the vitamins and minerals you consume. A number of vitamins and minerals have been linked to a lower risk of colon cancer, though results have been mixed. Studies haven't proved certain vitamins and minerals will stop you from getting colon cancer, but it can't hurt to vary the fruits and vegetables in your diet to ensure you get a wide selection of nutrients. Vitamins and minerals linked to a lower incidence of colon cancer include vitamin B-6 (pyridoxine), calcium, folic acid and magnesium.

Food sources of calcium include skim or low-fat milk and other dairy products, shrimp, tofu and sardines with the bones. Magnesium is found in leafy greens, nuts, peas and beans. Food sources of vitamin B-6 include grains, legumes, peas, spinach, carrots, potatoes, dairy foods and meat. Folic acid is the synthetic form vitamin B-9, and it's used in fortified breads, cereals and supplements. Vitamin B-9 occurs naturally in dark leafy greens such as spinach and lettuce, and in legumes, melons, bananas, broccoli and orange juice.

Limit alcohol consumption. Limit the amount of alcohol you drink to no more than one drink a day for women and two for men. A drink is a 4- to 5-ounce glass of wine, a 12-ounce can of beer, or a 1.5-ounce shot of 80-proof liquor.

Stop smoking. Talk to your doctor about ways to quit that may work for you. Stay physically active and maintain a healthy body weight. Try to get at least 30 minutes of exercise on most days. If you've been inactive, start slowly and build up gradually to 30 minutes. Also, talk to your doctor before starting any exercise program54.

Non-steroidal anti-inflammatory drugs seem to be the most promising drug for prevention of colon cancer; case-control and prospective cohort studies strongly suggest they reduce the risk of colon cancer. This is further supported by studies in familial cancer patients and animal data. However, this effect of non-steroidal anti-inflammatory drugs is unproved in randomized controlled trials, and the issue remains to be addressed. Immunotherapy seems to be well tolerated and effective in an adjuvant setting in colon cancer with limited residual disease. Its effect in stage II disease is comparable to that of adjuvant chemotherapy in Duke's C colon cancer. In more advanced disease it may have a role in combination with chemotherapy, and this approach is being explored in ongoing trials.

Gene therapy for colon cancer is still at an early stage of development. Preclinical studies have prompted several phase I trials. However, significant problems remain, such as low efficiency in gene transfer and the inhibitory effect of the host immunity, which may be addressed by developments in vector technology. As our understanding of the molecular biology of cancer increases, gene therapy is likely to have an increasingly important role in the expanding array of treatment options for colon cancer.

Dietary modifications to reduce the incidence of colon cancer may be difficult to implement (dietary interventional studies have shown this to be the case for cardiovascular disease); the roles of screening, chemotherapy, and radiotherapy have been covered earlier in this series 55.