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Colon Cancer Risk Factors

Causes

In most cases of colon or rectal cancers, the cause or causes are unknown. Defects in genes that normally protect against cancer play the major role in causing polyp cells to change and become cancerous. Some of these cases are caused by inherited genetic defects, and such patients usually have family histories of colorectal cancer. Most of the genetic mutations involved in colon cancers, however, appear to arise spontaneously (no strong family history) rather than being inherited. In such cases, environmental or other factors may trigger genetic changes in the intestine that lead to cancer.

Risk Factors and Prevention

Colorectal cancer is the third most common cancer in the U.S., with Americans facing a lifetime chance of 5 - 6% for this cancer. Each year, about 141,000 Americans are diagnosed with colorectal cancer, and about 49,000 people die from the disease. About 72% of these cancers occur in the colon and 28% in the rectum.

Rates of colorectal cancer have been decreasing in the United States. This is due in part to more people getting regular screenings for colorectal cancer, and fewer people engaging in risk factors such as smoking.

Colorectal cancer risk increases with age. More than 90% of these cancers occur in people over age 50.

Men have a slightly higher risk than women for developing colorectal cancer.

African-Americans have the highest risk of being diagnosed with, and dying from, colorectal cancer. Among Caucasians, Jews of Eastern European (Ashkenazi) descent have a higher rate of colorectal cancer. Asian Americans/Pacific Islanders, Hispanics/Latinos, and American Indians/Alaska Natives have a lower risk than Caucasians.

About 20 - 25% of colorectal cancers occur among people with a family history of the disease. People who have more than one first-degree relative (sibling or parent) with the disease are especially at high risk. The risk is even higher if the relative was diagnosed with colorectal cancer before the age of 60.

A small percentage of patients with colorectal cancer have an inherited genetic abnormality that causes the disease. Syndromes associated with genetic mutations include familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer.

  • Familial Adenomatous Polyposis (FAP). Familial adenomatous polyposis is caused by mutations in a gene called the adenomatous polyposis coli (APC) gene, which normally helps suppress tumor growth. In its defective form, it accelerates cell growth leading to polyps. The APC mutation can be inherited from either parent. People with FAP develop hundreds to thousands of polyps to in the colon. If FAP is left untreated, virtually everyone who inherits this condition develops cancer by age 45. Polyps usually first appear when people are in their mid-teens. FAP also increases the risks for other types of cancers including stomach, thyroid, pancreatic, liver, and small intestine cancers.
  • Hereditary Nonpolyposis Colorectal Cancer (HNPCC). Hereditary nonpolyposis colorectal cancer (HNPCC) is also known as Lynch syndrome. About 50 - 80% of people who inherit the abnormal gene develop colon cancer by age 45. HNPCC is caused by mutations in MLH1, MSH2, MSH6, and PMS2 genes. People with HNPCC are prone to other cancers, including uterine and ovarian cancers, as well as cancers of the small intestine, liver, urinary tract, and central nervous system.

The risks for colon cancer are far higher in industrialized nations than less developed countries. A Western lifestyle, being sedentary, smoking, and having excess weight have all been associated with increased risk for colorectal cancer. However, about 75% of cases occur without a known predisposing factor.

Dietary Factors. A diet high in red and processed meats increases the risk for colorectal cancer. Diets high in fruits and vegetables appear to be associated with reduced risk. Several major studies indicate that high consumption of dietary fiber protects against colorectal cancer, but other studies report little benefit. It is also not clear whether there is an association between colorectal cancer risk and deficiencies of vitamins such as folic acid, a type of vitamin B. Recent studies have shown that taking folic acid supplements do not lower the risk of developing colorectal cancer, and that high-dose supplements appear to increase the risk for recurrent polyp formation.

Alcohol and Smoking. Alcohol use and smoking are associated with an increased risk for colorectal cancer. Patients who smoke and drink may also be diagnosed with colorectal cancer at a younger age than non-drinkers and non-smokers.

Obesity. Obesity is associated with an increased risk for colorectal cancer, especially for men.

Physical Inactivity. A sedentary lifestyle increases the risk of developing colorectal cancer. Regular exercise may help reduce risk.

Adenomatous Polyps. People who have had adenomatous polyps (adenomas) have an increased risk of developing colorectal cancer. When these polyps are detected during colorectal screening, as colonoscopy, they can be removed before they turn cancerous.

Inflammatory Bowel Disease. Inflammatory bowel diseases include Crohn's disease and ulcerative colitis. The long-term inflammation caused by these chronic disorders can increase the risk for colorectal cancer. Inflammatory bowel disease (IBD) is not the same as irritable bowel syndrome (IBS). IBS does not increase colorectal cancer risk.

Diabetes. Many studies have identified an association between type 2 diabetes and colon cancer. Both diseases share common risk factors of obesity and physical inactivity, but diabetes itself is a risk factor for colorectal cancer.

The best way to prevent colorectal cancer is to engage in a healthy lifestyle: Exercising regularly, eating a healthy diet low in meat and high in fruits, vegetables, and whole grains may help reduce the risk for colon cancer. Do not smoke, and do not drink alcohol in excess. It is also important to have regular colorectal cancer screenings. [See Diagnosis and Screening section.]

Researchers have been investigating other possible protective measures. These include:

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs). Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used pain relievers that are available over-the-counter and by prescription. They include aspirin, ibuprofen (Advil, Motrin, generic), naproxen (Aleve, generic), and the COX-2 inhibitor celecoxib (Celebrex). Several studies have reported that NSAIDs help reduce the risk of colorectal cancer. However, regular use of non-aspirin NSAIDs, even in low doses, can increase the risk of gastrointestinal bleeding and stomach ulcers. Long-term use of NSAIDs can also increase the risk for heart attack and stroke, especially in people who have a history of heart disease.

The U.S. Preventive Services Task Force (USPSTF) does not recommend the routine use of aspirin or other NSAIDs to prevent colorectal cancer in people at average risk for this disease. (This recommendation does not apply to people who have a family history of colorectal cancer or who are at high risk for developing colorectal cancer due to other risk factors.) Due to the risks of regular use of these drugs, the American Cancer Society and other professional associations also recommend against the use of NSAIDs, or other types of medications, for primary colorectal cancer prevention.

There is some evidence that aspirin therapy may be helpful as secondary prevention after a diagnosis of colorectal cancer. Recent studies have suggested that regular aspirin use may help improve the chances of survival in patients diagnosed with colorectal cancer. In one important study, patients with early and advanced stage (stages I, II, and III) colorectal cancer who regularly took aspirin survived longer than those who did not take aspirin. However, even a low dose of daily aspirin has risks, including gastrointestinal bleeding. If you have been diagnosed with colorectal cancer, discuss with your doctor whether you should take aspirin and, if so, how much and how often.