Inherited and Acquired Risk Factors for Rectal and Colon Cancer

Who is at risk of developing colon cancer?

The development of colorectal cancer is complex interplay of  acquired and inherited factors. It should be noted that not every person with one or more of the risk factors will develop cancer of the colon and/or rectum. High risk patients, however, should be vigilant, undergo routine screening and undertake any lifestyle measures that may reduce the risk.

Age

The most important risk factor is age. The peak age of incidence is 60 to 79 years of age. The epidemiological studies show that there is a 0.5 to 2% chance that an unscreened individual aged above 50 years may have colon cancer and there is also a similar chance for carcinoma-in-situ of the colon (precancerous stage). The same group has 7 to 10% chance of harboring large adenomatous polyps of the colon, which can turn malignant in some individuals.

Lifestyle and dietary factors

High Calorie and Low Fat

High calorie consumption and obesity are found to increase the risk of colon cancer by two-fold in men. The modern western diet which is rich in fat and deficient in fiber is strongly associated with cancer of colon and countries where these dietary habits are predominant have a higher prevalence of colon cancer. The spread of western dietary practices to areas of low incidence has seen a rise in colon cancer within these population groups.

Meat

Consumption of red meat especially in the form of fried, grilled, barbecued or processed meat has shown to increase the risk of colon cancer. The fat in the red meat is believed to be metabolized into carcinogens by the colonic bacteria leading to abnormal proliferation of the colonic epithelium.

Fruit and Vegetables

Diets which are rich fiber content like wheat bran, fruits and vegetables are believed to reduce the risk of colon cancer. The fruit and vegetable-rich diet is believed to have preventive benefits and offers some protection from development of colon cancer. The benefits from fruits and vegetables are believed to come from antioxidants like vitamin A, C and E, folate, plant phenols, terpenes and the different types of fiber.

Calcium

Calcium is known to have a protective effect against colon cancer. It is believed to result from the ability of calcium to bind to the injurious bile acids and lead to reduction in proliferation of colonic epithelium.

Tobacco, Alcohol and Drugs

Heavy use of tobacco and alcohol are associated with higher risk of colon cancer. Regular use of aspirin and other NSAIDs have been shown to reduce the risk of colon cancer.

Physical Activity

Physical inactivity or a sedentary lifestyle can increase the risk of colon cancer while physical activity can reduce risk of colon cancer. It has also been found that cancer-related mortality was reduced following increased physical activity after the diagnosis of non-metastatic colon cancer. Physical activity has also been found to reduce the risk of recurrence following resection of operable colon cancers.

Hereditary factors

Colon cancer has strong familial predisposition. There is a 2 to 3 fold increase in the risk of colon cancer in individuals having a first-degree relative with colon cancer. The risk further doubles when two first-degree relatives are affected with colon cancer. Some sporadic colon cancers are also found to be associated strongly with hereditary susceptibility but are more likely to occur in the backdrop of one of more of the dietary or lifestyle factors mentioned above.

Premalignant conditions

Colon polyps

These conditions are discussed further under intestinal polyps.

• Familial adenomatous polyposis (FAP) is a familial precancerous condition that can lead to colon cancer. About 1% of colon cancers develop from numerous adenomatous polyps present in FAP patients that eventually turn malignant.
• MYH-Associated polyposis (MAP) is similar to FAP but there is no detectable APC gene mutation and instead they present with MYH-gene mutation.
• Hereditary non-polyposis colon cancer (HNPCC) accounts for about 3% of all colon cancers and it results from mutations in human DNA mismatch repair genes that result in microsatellite instability (MSI).
• Rare hamartomatous polyposis syndromes like Peutz-Jeghers Syndrome and Juvenile polyposis affects young individuals. These syndromes increase risk of colon cancer and accounts for less than 1% of colon cancers.

Inflammatory bowel disease

Inflammatory bowel disease like Crohn’s disease and Ulcerative colitis are known to increase the risk for colon cancer. There is a 10 to 20 fold increased risk for colon cancer among individuals with ulcerative colitis and the Crohn’s disease increases the risk by 4 to 6 times. About 2 to 4% of all patients suffering from ulcerative colitis develop colon cancer.

Other

• Long-standing ureterosigmoidostomy of 15 years or more is known to increase the risk of colon cancer by about 10%.
• Other conditions predisposing to colon cancer include individuals diagnosed with Streptococcus bovis endocarditis or septicemia.