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Chapter 1 - Epidemiology, risk factors and pathogenesis

Colorectal Cancer

CRC is the third most common cancer worldwide, and the second leading cause of cancer death (1.8 million cases and 881 000 deaths in 2018).

Incidence and mortality rates vary geographically, with the highest rates in the most developed countries.
These rates are ~25% lower in women than in men.

An overall decline or stabilisation in the risk of CRC has been noted in high-income countries. In contrast, a worrying rise has been observed in patients <50 years old.

10%-20% of CRCs occur in people with positive family history, with varying risk depending on the number and degree of affected relatives.

About 5%-7% of cases are affected by hereditary conditions. The two major ones are hereditary nonpolyposis colorectal cancer (HNPCC) and familial adenomatous polyposis (FAP).

Obesity, lack of physical activity and some dietary factors are the major lifestyle factors contributing to CRC risk, but the underlying causative processes are not defined.

CRC exemplifies stepwise progression as it develops initially as a benign precursor lesion (adenoma), which can progress to an invasive lesion (adenocarcinoma).

The lesion arises from an intestinal clonogenic precursor cell through the accumulation of multiple genetic abnormalities. There are three major precursor lesion pathways: the chromosomal instability (conventional) pathway (~80%), the microsatellite instability pathway (2%-7%) and the sessile serrated (CpG island methylator, ~15%).

Revision Questions

  1. What are the trends in CRC risk in high-income countries?

  2. What are the most important modifiable risk factors of CRC?

  3. Which is the most common precursor lesion pathway of CRC?
Gastric Cancer Pancreatic Cancer

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