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