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Key Clinical Updates in Colorectal Cancer

Meta-analyses suggest that individuals with increased physical activity are up to 27% less likely to develop colon cancer. Also, for each increase of 5 kg/m2 in BMI, there is a 5% increased cancer risk.

Colonoscopy should be considered in all nonmenstruating adults with new-onset iron deficiency anemia.


  • Personal or family history of adenomatous or serrated polyps or colorectal cancer are important risk factors.

  • Symptoms or signs depend on tumor location.

  • Proximal colon: fecal occult blood, anemia.

  • Distal colon: change in bowel habits, hematochezia.

  • Diagnosis established with colonoscopy.


Colorectal cancer is the second leading cause of death due to malignancy in the United States. Colorectal cancer will develop in approximately 4.2% of Americans and has a 5-year survival rate of 65%. In 2019, there were an estimated 145,600 new cases of colorectal cancer in the United States, with an estimated 51,020 deaths. Between 1996 and 2010, its mortality rate decreased by 46%. A 2015 National Health Interview Survey estimated that 62% of US adults have undergone recommended screening. On average, new cases have been falling 3.2% each year over the last 10 years.

Colorectal cancers are almost all adenocarcinomas, which tend to form bulky exophytic masses or annular constricting lesions(eFigure 39–7). The majority of colorectal cancers are thought to arise from malignant transformation of an adenomatous polyp (tubular, tubulovillous, or villous adenoma) or serrated polyp (hyperplastic polyp, traditional serrated adenoma, or sessile serrated adenoma). Polyps that are “advanced” (ie, polyps at least 1 cm in size, adenomas with villous features or high-grade dysplasia, or serrated polyps with dysplasia) are associated with a greater risk of cancer. Approximately 85% of sporadic colorectal cancers arise from adenomatous polyps. They 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). Activation of oncogenes such as KRAS and BRAF is present in a subset of colorectal cancers with prognostic and therapeutic implications discussed further below.

eFigure 39–7.

Colonic adenocarcinoma that is circumferential and narrowing the lumen. (Used, with permission, from Y. Chen.)

Approximately 10–20% of colorectal cancers arise from serrated polyps, most of which have hypermethylation of CpG-rich promoter regions that leads to inactivation of the DNA mismatch repair gene MLH1, resulting in microsatellite instability, and activation of mutations of the BRAF gene. Serrated colon cancers have distinct clinical and pathologic characteristics, including diploid DNA content, predominance in the proximal colon, poor differentiation, and more favorable prognosis.

Up to 5% of colorectal cancers are caused by inherited germline ...

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