Colorectal cancer General Considerations

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Colorectal cancer is the second leading cause of death due to malignancy in the United States. Approximately 6% of Americans will develop colorectal cancer and 40% of those will die of the disease. An estimated 145,000 new cases and 55,000 deaths occur annually. Colorectal cancers are almost all adenocarcinomas, which tend to form bulky exophytic masses or annular constricting lesions.

Slightly less than 50% of cancers are located distal to the splenic flexure (within the descending colon or rectosigmoid region), where they are within reach of detection by flexible sigmoidoscopy. There appears to be a gradual increase in incidence of cancers in the cecum and ascending colon, and over half of cancers now develop proximal to the splenic flexure.

It is currently believed that the majority of colorectal cancers arise from malignant transformation of an adenomatous polyp. Approximately 85% of sporadic colorectal cancers have loss of function of one or more tumor suppressor genes (eg, p53, APC, or DCC) due to a combination of spontaneous mutation of one allele combined with chromosomal instability and aneuploidy (abnormal DNA content) that leads to deletion and loss of heterozygosity of the other allele (eg, 5q, 17q, or 18p deletion). 

Approximately 15% of colorectal cancers have microsatellite instability due to inactivation of DNA mismatch repair genes. This is most commonly an acquired defect caused by hypermethylation of the promoter region of the MLH1 gene, but may be an indicator of unrecognized HNPCC. Colon cancer with high microsatellite instability have distinct clinical and pathologic characteristics, including diploid DNA content, predominance in the proximal colon, poor differentiation, and more favorable prognosis.

ESSENTIALS OF DIAGNOSIS

• Symptoms or signs depend on tumor location.

• Proximal colon: fecal occult blood, anemia.

• Distal colon: change in bowel habits, hematochezia.

• Characteristic findings on barium enema or CT colonography.

• Diagnosis established with colonoscopy.

Rebecca A. Barnetson and Malcolm G. Dunlop
Colon Cancer Genetics Group, University of Edinburgh, School of Molecular and Clinical Medicine and MRC Human Genetics Unit, Western General Hospital, Edinburgh, U.K.

References

RELATED STORIES:
Colorectal Cancer Classification Systems   Colorectal Neoplasms Follow-Up after Surgery and Prognosis   Carcinoma of the Anus   Colorectal cancer management   Colonic or Rectal cancer Treatment   Risk factors for colorectal Neoplasia   Colorectal Cancer Treatment   Screening for Colorectal Neoplasms   Variations in Incidence Within Countries: Epidemiology of Colorectal Cancer   Management of patients who present with Synchronous distant metastases   Colorectal Cancer Prognosis and Prevention   Surgical Management of Colorectal Cancer   Colorectal cancer Risk Factors   Anorectal Cancer   Epidemiology of Colorectal Cancer   Groups at increased risk of colorectal cancer   Family history may impact on the folate–colon cancer relationship   Colorectal Cancer Incidence, Location, Anatomy and Pathogenesis   Colorectal Cancer   Hereditary nonpolyposis colorectal carcinoma   Diagnosis and Screening for Colorectal Cancer   Colorectal cancer Clinical Findings and Differential Diagnosis

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