Last month I discussed the genetics of Hereditary Breast and Ovarian Cancer syndrome as it relates to who should and should not be tested and what should be done with that information. While BRCA-1 and BRCA-2 are significantly important to the genetics of Breast Cancer, they are certainly not the only genetic mutations that can cause cancer. I want to focus this month on a condition known as Lynch Syndrome or Hereditary Non-polyposis Colorectal Cancer (HNPCC). This is a condition where several, seemingly unrelated cancers, will cluster in families.
When the body grows and develops, each cell will duplicate the genetic code, or DNA. In order to ensure an exact copy is made, the body has “proof-reading” genes which will correct mistakes. The three main genes that correct errors and mistakes are MLH-1, MSH-2, and MSH-6. If these genes are mutated then mistakes will be allowed to occur when the genetic code duplicates. These mistakes will occur in every cell of the body and increase the risk of cancer.
Since this mutation can be passed on either side of a family, it is critical to look at the family history in order to determine if a patient should be tested for Lynch syndrome. The cancers that are associated with Lynch syndrome include colon, endometrial, ovarian, gastric, small bowel, gallbladder, brain, renal pelvis, sebaceous adenoma and pancreas. Any patient with a family member diagnosed with colon or endometrial cancer before age 50 or any two family members with any of the above cancers may have the syndrome.
If a patient is positive for the genetic mutation then the risk of colon cancer increases to 82% and endometrial cancer increases to 71%. As much as 50% of female patients with the mutation will present with a gynecologic cancer before a colorectal cancer. Since the risk of cancer is so high, the early identification of the mutation can allow for early screening and intervention to prevent the cancers.
While all patients need to be screened for colon cancer starting at age 50, certain high risk individuals are screened earlier then age 50. A Lynch positive patient needs to have colonoscopies and endoscopies every single year to allow for the early detection of a precancerous polyp. The reason for this is that cancer develops quickly and aggressively. While the average polyp may take 5 or more years to become cancerous, a polyp in Lynch syndrome can become cancerous in 18 months. Ultimately, some patients may require surgery to remove the large intestine and gallbladder to dramatically reduce cancer risk. The uterus and ovaries should be screened as well but, unfortunately, few to no screening tests exist that are as effective as surgical intervention. The best option is a hysterectomy and removal of the ovaries.
In conclusion, any family history of cancer should be properly evaluated by a knowledgeable physician to detect the risk for genetic disorders. The test requires a simple tube of blood sent to the proper lab for processing. This can be done at any physician’s office that is trained in the evaluation of genetic disorders. The proper application of these tests and detection of the mutation can allow for interventions which will prevent cancer and ultimately, save lives.
