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The Genetics of Colorectal Cancer

Paula M. Calvert, MD; and Harold Frucht, MD
[+] Article and Author Information

From Fox Chase Cancer Center, Philadelphia, Pennsylvania; and College of Physicians and Surgeons, Columbia University, New York, New York.


Acknowledgments: The authors thank Kathy Buchheit and Ellen Ragan for editorial and administrative support. They also thank Alfred G. Knudson, MD, PhD, for ongoing teaching, insight, and support; for careful review of the manuscript; and for helpful suggestions.

Grant Support: By the National Cancer Institute (CA 70335) (Dr. Frucht).

Requests for Single Reprints: Harold Frucht, MD, Division of Digestive and Liver Diseases, College of Physicians and Surgeons, Columbia University, 630 West 168th Street, Box 83, New York, NY 10032.

Current Author Addresses: Dr. Calvert: Tullamore General Hospital, Arden Road, Tullamore, County Offaly, Ireland.

Dr. Frucht: College of Physicians and Surgeons, Columbia University, Division of Digestive and Liver Diseases, 630 West 168th Street, Box 83, New York, NY 10032.


Ann Intern Med. 2002;137(7):603-612. doi:10.7326/0003-4819-137-7-200210010-00012
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Colon cancer is a common disease that can be sporadic, familial, or inherited. Recent advances have contributed to the understanding of the molecular basis of these various patterns of colon cancer. Germline genetic mutations are the basis of inherited colon cancer syndromes; an accumulation of somatic mutations in a cell is the basis of sporadic colon cancer; and, in Ashkenazi Jewish persons, a mutation that was previously thought to be a polymorphism may cause familial colon cancer. Mutations of three different classes of genes have been described in colon cancer etiology: oncogenes, suppressor genes, and mismatch repair genes. Knowledge of many of the specific mutations responsible for colon carcinogenesis allows an understanding of the phenotypic manifestations observed and forms the basis of genetic testing for inherited disease. Although genetic testing is possible and available, it is only an adjunct to the clinical management of persons at risk for colon cancer and patients with colon cancer. As a result of advances in the understanding of the molecular causes of colon cancer and the availability of colon cancer screening methods such as colonoscopy, it should be possible to prevent the vast majority of colon cancer in our society. Practicing clinicians should recognize the patterns of clinical colon cancer, understand its causes, and be able to use genetic testing and endoscopic screening for prevention.

Figures

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Figure 1.
The normal function of the different classes of cancer-causing genes according to cell-cycle stage.5

Modified and reprinted with permission from reference . Copyright 1998 by the American Society of Clinical Oncology.

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Figure 2.
Loss of suppressor-gene function.5

Modified and reprinted with permission from reference . Copyright 1998 by the American Society of Clinical Oncology.

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Figure 3.
Familial colorectal cancer (CRC) andAPCgene mutation I1307K in Ashkenazi Jewish persons.5

Reprinted with permission from reference . Copyright 1998 by the American Society of Clinical Oncology.

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Figure 4.
Pedigree of a family meeting the Amsterdam criteria for hereditary nonpolyposis colorectal cancer.

Inheritance is from the proband's paternal family. Black shading indicates cancer. BL = bladder cancer; BO = bone cancer; CO = colon cancer; EN = endometrial cancer; RE = rectal cancer.

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Figure 5.
Laboratory methods for detection of gene mutations, according to the nucleic acid or protein tested.5

Although sensitivities for each test vary by laboratory and the specific gene involved, some indication of utility is given for each test. DGGE = denaturing gradient gel electrophoresis; mRNA = messenger RNA; MSI = microsatellite instability; SSCP = single-strand conformational polymorphism. Modified and reprinted with permission from reference . Copyright 1998 by the American Society of Clinical Oncology.

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Figure 6.
Algorithm for a clinical approach to inherited colon cancer syndromes.

FAP = familial adenomatous polyposis; HNPCC = hereditary nonpolyposis colorectal cancer.

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Summary for Patients

The Genetics of Colorectal Cancer

The summary below is from the full report titled “The Genetics of Colorectal Cancer.” It is in the 1 October 2002 issue of Annals of Internal Medicine (volume 137, pages 603-612). The authors are PM Calvert and H Frucht.

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