Causes of colon cancer
Approximately 6 percent of the American population will eventually develop advanced colorectal cancer. The good news is that if detected early, colon cancer can be cured by surgery alone. Even better news—unlike most cancers, cancer from the colon and rectum can be completely prevented. Therefore, the U.S. Task Force on Cancer Prevention and many other professional societies have recommended screening for colon cancer.
In the vast majority (75 percent) of patients with colon cancer, there is no positive family history. While genetic defects are likely to contribute to cancer information, the causes are unknown. Acquired genetic alterations during the progression from benign to premalignant polyps and subsequent cancer frequently include several alterations of oncogenes and tumor suppressor genes such as the RAS oncogene, the APC gene, the p53 tumor suppressor gene and the DCC (Deleted in Colon Cancer) gene.
In 25 percent of colon cancers, a hereditary cause can be identified or assumed. In about 1 percent of these cases, the cancer is caused by alterations of the APC gene, a possible tumor suppressor gene with a gene frequency in the population of 1:10,000 to 1:20,000. This condition is called Familial Adenomatoues Polyposis (FAP). Patients with FAP begin to develop hundreds of polyps in the colon in their teenage years, and most will have developed cancer by age 40.
In about 4 percent of the cases, the cancer is caused by mismatch repair genes with a much higher gene frequency in the population of 1:200 to 1:1000; these are genes that help repair the genetic material, DNA, and if defunct, they cause genetic alterations and tumor growth. This condition is called Hereditary Non-Polyposis Colon Cancer. In this genetic colon cancer syndrome, multiple direct and indirect family members across several generations are affected at an early age.
In 20 percent of the hereditary cases, one or more family members have had colon cancer. In these families, the genetic defect(s) have not been unequivocally identified.
Prevention: low-fat diet
It is clear that dietary factors are important. A diet high in fats, cholesterol, fried foods and low in fiber is associated with a higher rate of colon cancer, while a diet high in fruits and vegetables as well as exercise are associated with a lower colon cancer rate. Countries with high fat intake, such as the United States and Australia, have a high colon cancer rate, while countries with low fat intake, such as Japan and the Philippines, have a lower rate.
Observational data also indicates that aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), vitamins A, C, & E, calcium, fiber and selenium may have a protective effect.
Finally, colon cancer screening via colonoscopy can prevent cancer by identifying polyps—precancerous growths that often resemble the shape of mushrooms.
Four screening methods are currently available, but recent recommendations have made some screening methods almost obsolete.
- Testing the stool for occult (invisible) blood reduces the cancer death rate by 30 percent. Like breast self-examination, this test is easy, safe and inexpensive, but most early cancers and pre-cancerous polyps are not detected. If the test is positive, colonoscopy is needed.
- Barium enema examination detects about 50 percent of larger polyps and most advanced cancers but misses smaller polyps and cancers. In most instances, this test is not covered by insurance for the purpose of colon cancer screening.
- Flexible sigmoidoscopy examines about 40 percent of the colon well with high accuracy and detects up to 60 percent of polyps and cancers but leaves the right colon unexamined; this would be similar to performing mammograms of the left breast only. In the case of abnormal findings on fecal occult blood testing, barium enema examination or sigmoidoscopy, complete colonoscopic evaluation is needed.
- Colonscopy examines 100 percent of the colon with high accuracy. *This is the only examination that can prevent colon cancer by detecting polyps (precancerous tumor growths).
While recommendations for colorectal cancer screening have undergone significant changes and not all questions have been answered, most authorities recommend screening with colonoscopy as the preferred and most accurate screening tool. In average-risk people and in patients without a history of a familial colon cancer syndrome such as FAP or HNPCC, screening with colonoscopy should begin at about age 50 and every 8-10 years thereafter.
In patients with a family history of FAP, genetic testing and/or sigmoidoscopy should begin in their early teens. In patients with HNPCC, screening should begin in their early thirties or even twenties by colonoscopy and every other year thereafter. In special situations, such as in patients with ulcerative colitis or Crohn’s disease, screening with colonoscopy should begin 8-15 years after the onset of the inflammatory bowel disease, depending upon extent of colonic involvement.
While advances in laparoscopic surgery and new chemotherapeutic agents will improve disease outcome, the emphasis must remain on colon cancer prevention and screening.
Genetic testing in familial colon cancer syndromes is already available. Molecular screening tests that detect abnormalities in tumor suppressor and oncogenes from stool specimens are under investigation. While the video capsule swallowed by mouth detects lesions in the small bowel, it is not useful for the evaluation of the colon at this time.
CT colography, frequently referred to as virtual colonoscopy, is not yet considered the standard of care for colon cancer screening or the detection of other colonic disease.
However, this test shows the most promise for screening purposes and if perfected, may replace colonoscopy, which is highly accurate but somewhat invasive as a screening tool.
Colonoscopy is the only screening test that can detect and also prevent colon cancer by identifying polyps early on. It will likely remain the test of choice for colorectal cancer screening for some time to come.
by H. Jurgen Lenz, MD, Gastroenterology, Scripps Memorial Hospital La Jolla