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Colon and rectal cancers - Causes

Description

An in-depth report on the causes, diagnosis, treatment, and prevention of colorectal cancer.

Alternative Names

Colorectal cancer

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 continuously spread 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 trigger genetic changes in the intestine that lead to cancer.

Inherited Genetic Factors

A small percentage of cases of colon cancer are due to inherited factors. The two most common colorectal cancer syndromes associated with genetic mutations are familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer (HNPCC). Genetic tests can help screen for mutations associated with these syndromes.

Familial Adenomatous Polyposis (FAP). Familial adenomatous polyposis is caused by mutations in a tumor suppressor gene called APC. When the adenomatous polyposis coli (APC) gene is normal, it 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. FAP causes less than 1% of all cases of colorectal cancer. If FAP is left untreated, however, virtually everyone who inherits this condition develops cancer by age 45. Polyps usually first appear when people with FAP 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), also known as Lynch syndrome, accounts for 3 - 5% of all colorectal cancers. 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.

Resources

www.cancer.org -- American Cancer Society
www.cancer.gov -- National Cancer Institute
www.asco.org -- American Society of Clinical Oncology
www.cancer.net -- Cancer.Net
www.nccn.org -- National Comprehensive Cancer Network
www.fightcolorectalcancer.org -- Colorectal Cancer Coalition
www.cancer.gov/clinicaltrials -- Find clinical trials

References

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Johnson CD, Chen MH, Toledano AY, Heiken JP, Dachman A, Kuo MD, et al. Accuracy of CT colonography for detection of large adenomas and cancers. N Engl J Med. 2008 Sep 18;359(12):1207-17.

Jonker DJ, O'Callaghan CJ, Karapetis CS, Zalcberg JR, Tu D, Au HJ, et al. Cetuximab for the treatment of colorectal cancer. N Engl J Med. 2007 Nov 15;357(20):2040-8.

Karapetis CS, Khambata-Ford S, Jonker DJ, O'Callaghan CJ, Tu D, Tebbutt NC, et al. K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med. 2008 Oct 23;359(17):1757-65.

Kim DH, Pickhardt PJ, Taylor AJ, Leung WK, Winter TC, Hinshaw JL, et al. CT colonography versus colonoscopy for the detection of advanced neoplasia. N Engl J Med. 2007 Oct 4;357(14):1403-12.

Kuhry E, Schwenk WF, Gaupset R, Romild U, Bonjer HJ. Long-term results of laparoscopic colorectal cancer resection. Cochrane Database Syst Rev. 2008 Apr 16;(2):CD003432.

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Levin B, Lieberman DA, McFarland B, Smith RA, Brooks D, Andrews KS, et al. Screening and surveillance for the early detection of colorectal cancer and adenomatous polyps, 2008: a joint guideline from the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology. CA Cancer J Clin. 2008 May-Jun;58(3):130-60. Epub 2008 Mar 5.

Moghaddam AA, Woodward M, Huxley R. Obesity and risk of colorectal cancer: a meta-analysis of 31 studies with 70,000 events. Cancer Epidemiol Biomarkers Prev. 2007 Dec;16(12):2533-47.

National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Colon Cancer. V.3.2008

National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Rectal Cancer. V.3.2008.

U.S. Preventive Services Task Force. Routine aspirin or nonsteroidal anti-inflammatory drugs for the primary prevention of colorectal cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2007 Mar 6;146(5):361-4.

U.S. Preventive Services Task Force. Screening for colorectal cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2008 Nov 4;149(9):627-37. Epub 2008 Oct 6.

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Reviewed last on: 12/1/2008
Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.

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