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COLORECTAL CANCER

http://meddev.uio.no/elaring/lcms13/ernaeringslaere/nutr-cancer-epidemiology/illustrations/colon.jpg

Descriptive Epidemiology

See chapter 7.9 page 280 in WCRF/AICR Food, Nutrition, Physical Activity, and the Prevention of Cancer: a Global Perspective.

pdf Cancers

1 million new cases in 2002.

Incidence and mortality from this cancer is in general increasing, especially in developed world and in urban areas of developing world.

High risk areas: North America, Europe and Australia. The developed world accounts for over 60% of the incidence. Low risk areas: Central and South America, Asia and Africa.

5-year survival rates are 50-60%.

One of two main cancers believed to be modified mainly by food and nutrition.

Colon cancer – similar incidence in men and women.

Rectal cancer – more common in men.

98% are adenocarcinomas.

Rectal tumours now only about 27%, 50% proximal to the splenic flexure.

Etiology in general similar for the two types.

http://meddev.uio.no/elaring/lcms13/ernaeringslaere/nutr-cancer-epidemiology/illustrations/incidence_2008_colorectal.jpg

Pathogenesis:

Initial lesion is a benign adenomatous polyp.

Undergoes further disorganization of cellular and tissue phenotype and ultimately becomes a carcinoma.

The molecular basis for the adenoma/carcinoma development is well described:

  • complex multistep process with increasing alterations of multiple genes that control cell growth and differentiation. (More on colorectal cancer development in Nutrition and Cancer Biology.)
  • Some events occur early: mutation or loss of the APC gene, mutation of K-ras, and general disorganisation of DNA methylation
  • Some events occur late: loss of p53

Genetic syndromes that increase the risk of colorectal cancer:

Familial adenomatous polyposis (FAP, also called adenomatous polyposis coli, APC)

  • multiple colonic adenomas (from a few to thousands)
  • Adenomas can occur at a young age
  • Associated with mutations in the APC gene
  • Almost 100% risk of developing colon adenocarcinomas, but represent only a small % of all colon cancers!

Hereditary non-polyposis colorectal cancer (HNPCC)

  • No abundance of polyps
  • More common than FAP
  • Cancer has early onset
  • Syndrome associated with other cancers (endometrium, urinary tract, stomach, biliary system)
  • Associated with mutations in DNA mismatch-repair genes such as MSH2, MLH1, PMS1 and PMS2.