Tag Archives: genetics

Family Colon Cancer Syndromes. More common than you think.

Colorectal cancers can be divided into those cases that are attributed to a genetic syndrome or are sporadic. The majority of colorectal cancers are sporadic which means they occur without any obvious genetic predisposition. About 80% of all colorectal cancers are sporadic. What likely happens in sporadic colorectal cancer is that there is a mutation in a gene that causes the colon lining cells to evolve into a polyp and progress to a cancer. This sequence takes about 10-15 years. What triggers the mutation is not clearly understood but dietary and lifestyle behaviors probably play a role. For example, a diet high in red meat and low in fiber, lack of exercise, obesity, and smoking tobacco are risk factors. The recommendation of a screening colonoscopy beginning at age 50 is directed at detecting sporadic colorectal cancer. This assumes that one does not have a family history of colorectal cancer which may indicate a genetic colorectal cancer syndrome. If there is a family history of colorectal cancer, then one should undergo a screening colonoscopy at an age earlier than 50.

There are many hereditary colorectal cancer syndromes. It is important to identify patients with a hereditary colorectal cancer syndrome to ensure they and their families receive appropriate counseling and genetic testing. If one is diagnosed with a hereditary colorectal cancer syndrome, then specific medical management should be provided. I will address the two most common syndromes, Lynch Syndrome and Familial Adenomatous Polyposis (FAP).

Lynch Syndrome
Lynch Syndrome results from a genetic defect involving the loss of a gene known as the mismatch repair gene (MMR). Lynch Syndrome is the most common hereditary colorectal cancer syndrome and accounts for about 3-5% of all colorectal cancers. Individuals and affected family members are at risk for developing a number of cancers at an early age. These cancers include: colon, rectum, uterus, ovaries, stomach, small intestine, biliary tract, pancreas, kidney, ureter, bladder, and brain. The onset of cancer is about age 40. Interestingly, the colorectal cancers that arise in Lynch Syndrome do not develop in the setting of typical colon polyps. The colorectal cancer develops rapidly unlike the slow growth of a sporadic colorectal cancer that starts off as a colon polyp and slowly grows into a cancer.

A 3-question survey developed by Kastrinos et al. identifies individuals to a high degree of certainty with the gene mutation causing Lynch Syndrome. If the answer to the following 3 questions is ‘yes,’ then there is a 95% of having the gene mutation causing Lynch Syndrome.

  1. Do you have a first degree relative (sibling, parent, child) with any of the following cancers diagnosed before age 50: colon, rectum, uterus, ovaries, stomach, small intestine, biliary tract, pancreas, kidney, ureter, bladder, or brain?
  2. Have you had colorectal cancer or colon polyps diagnosed before age 50?
  3. Do you have more than 2 first degree relatives (sibling, parent, child) or second degree relatives (aunts, uncles, grandparents) with a history of colorectal cancer?

If you answer yes to the above questions, you should discuss this with your physician and pursue genetic counseling with a certified genetic counselor. If you have Lynch Syndrome, management includes the following:

  1. Colonoscopy every 1-2 years beginning at age 20-25, or 2-5 years earlier if the youngest affected relative was diagnosed before the age of 25.
  2. For women, annual pelvic examination, transvaginal ultrasound, and endometrial sampling.
  3. Upper endoscopy every 2-3 years beginning at age 30-35.
  4. Hysterectomy with removal of the ovaries and fallopian tubes for women who have finished child-bearing or at age 40.

Familial Adenomatous Polyposis (FAP)
FAP accounts for about 1% of cases of colorectal cancer. FAP is caused by a mutation in the APC gene. Patients with FAP typically have over 100 adenomatous polyps; the polyps typically begin growing in the teenage years. Virtually all patients will develop colorectal cancer if untreated. The average age of developing colorectal cancer in FAP if untreated is age 40. Patients with FAP are at risk for developing cancer of the duodenum (small intestine) and can also develop benign tumors of connective tissue that are known as desmoid tumors. Family members should be offered genetic counseling with a certified genetic counselor. Management recommendations for FAP include a yearly sigmoidoscopy beginning at age 12-14 and an upper endoscopy every 1-4 years to screen for duodenal cancer. Treatment for FAP involves removing the entire colon. A colostomy (with external bag) can be avoided with advanced surgical technique that creates a new rectum with the end of the small intestine. The new rectum is then sutured to the anus that allows one to have regular bowel movements. Treatment with medications known as COX-2 inhibitors or the anti-inflammatory Sulindac have been shown to help prevent polyp formation in FAP.

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Here’s to your colon health!

Signature of Dr. Farrell

Frank Farrell, MD, MPH, AGAF