Did you know that colorectal cancer (CRC) is the second leading cause of cancer deaths in this country among men and women combined and that 245,000 people in the U.S. were diagnosed with colorectal in 2017, with over 50,000 deaths that year from this disease? This year, more than 1 in 20 persons in this country will be diagnosed with CRC. Identification of individuals who are at a higher risk for development of CRC, screening those individuals, and testing their tumors for specific DNA mutations provides a better chance of early detection and cure.
Colorectal cancer is caused by both genetic and environmental factors. It develops over time from multiple, cumulative mutations of the genetic code (DNA) which can cause progressive changes of normal tissue into colon cancer, usually with colon polyps as an intermediate step. Not all colorectal cancers contain the same mutations, and some mutations confer a better prognosis than others. All cancers contain DNA mutations; however, most cancers are not inherited from one’s parents but develop from sporadic DNA mutations in the individual. Medical understanding of these cancers is ever increasing.
The approach of identifying specific DNA mutations in a tumor and its susceptibility to treatment is the essence of personalized medicine. As it turns out, up to 30% of CRCs have a specific mutation called KRAS. Unfortunately, many traditional cancer treatments are either less effective or ineffective when this mutation is present. However, with personalized cancer medicine, specific or “targeted” therapies are available for more effective cures.
Individuals with the following genetic diseases (syndromes) have elevated risk of CRC and should receive intensive follow-up by a gastroenterologist who can perform surveillance, and explain the disease course and treatment. Surveillance of family members is also needed.
- Familial Adenomatous Polyposis – Affected patients have a markedly increased risk of developing CRC, often at a very young age, sometimes before age 30.
- Hereditary Non-Polyposis Colorectal Cancer (also called “Lynch Syndrome”) – This is another inherited type of CRC with the average age of cancer development at 44 years. These patients are insensitive to commonly used chemotherapy drugs.
- 11307K (APC Ashkenazi) Mutation – This mutation is present in 6% of Ashkenazi (central and eastern European) Jewish descendants and confers a 2 to 5 time increased lifetime risk of CRC. Of historical interest, Ashkenazi ancestry has been found in Hispanic Catholics in northern New Mexico and southern Colorado, especially in the San Luis Valley.
- Peutz-Jeghers Syndrome – These patients have freckles around the lips and inside the mouth, polyps in the intestines, and increased risk for CRC.
- MYH-Associated Polyposis – This inherited condition is caused by an autosomal recessive genetic pattern, which means both parents must be carriers in order for their offspring to express the mutation’s impact.
Other risk factors for the development of CRC include a personal or family history of colon polyps or a history of colorectal cancer, increased alcohol consumption and tobacco use.
While many of the underlying genetic predispositions to CRC are understood, the environmental factors are still an active area of research. There is still debate about whether these risk factors actually cause DNA mutations or if they are simply associated with DNA mutations. Environmental associations include lack of regular physical activity, a diet low in fruit and vegetables, a low-fiber and high-fat diet, or being overweight or obese.
Finally, patients with inflammatory bowel disease (either ulcerative colitis or Crohn disease) have increased risk of CRC. The risk of CRC increases over time.
These patients should begin colonoscopy surveillance within 10 years of their diagnosis.
Getting the correct diagnosis and treatment is a concerted effort between your primary care physician, gastroenterologist, surgeon, radiologist, pathologist, oncologist, genetic counselor, and many other healthcare professionals. Reduce your risk by living a healthy lifestyle and undergoing standard screening to include a colonoscopy. If you know you are at increased risk, start your screening at an earlier age.
The National Cancer Institute has created a Colorectal Cancer Risk Assessment Tool for patients between the ages of 50 and 85. The tool applies to African Americans, Asian American/Pacific Islanders, Hispanic/Latinos, and Caucasian men and women. Click on the link to assess your risk for Colorectal Cancer. It will take about 8 minutes to complete. NOTE: This tool does not yet apply to American Indians and Alaska Natives or patients with ulcerative colitis, Crohn disease, Familial Adenomatous Polyposis, Hereditary Non-Polyposis Colorectal Cancer (Lynch Syndrome), or a personal history of CRC.