The Genetic link of Colorectal Cancer

It has long been understood  that having a family history of colorectal cancer increases an individual’s risk of developing the disease. In fact, many gastrointestinal diseases are inherited or have a genetic predisposition. In recent years, medical research has identified the specific genes responsible for some of these conditions.

“There is an inherited condition called polyposis in which people develop polyps throughout the colon, hundreds to thousands of them,” says Dr. Sunil Khurana, CEO of Premier Medical Group and director of the GI Division. “These people always develop colon cancer, that’s a given. Some of their family members, however, though they don’t have these multiple polyps, are likely to have a condition called hereditary non-polyposis colorectal cancer (HNPCC) or Lynch Syndrome, after the physician who characterized it.”

Most colon cancers are considered “sporadic,” that is, they occur without the presence of a genetic abnormality. But about 3-4 percent of colorectal cancers in the U.S. are due to Lynch Syndrome, and close to seven percent of people who develop the disease before the age of 50 have Lynch Syndrome (LS).

“The studies show that having Lynch Syndrome gives people an 80-85 percent risk of developing colorectal cancer in their lifetime,” says Khurana. “And LS is not only implicated in colorectal cancer, it is related to a very high incidence of uterine cancer. In fact, if you look at the women who develop uterine cancer before the age of 50, 9 percent of them have LS. This, and other considerations, has led physicians to recommend that the families of patients who develop colon cancer before age 50 be tested for LS.”

The recommendation for screening in the general population calls for colonoscopy to start at age 50 and be repeated every 8–10 years. “The thesis behind that is that even if you start developing a polyp the day after your colonoscopy, it takes a while for the polyp to develop and a long time for the polyp to turn into cancer,” Khurana says. “But in people who have Lynch Syndrome, that period is not 8–10 years, it can be in as little as 1-3 years. We need to screen the family members of people with LS at a much younger age than normal, starting at age 20-25, and screen them more frequently, perhaps every year to two years.”

New data coming out shows that the average age at which people develop Lynch Syndrome is 58. That has led some experts to suggest that testing be done for all people with colorectal cancer, not just those who develop cancer before age 50. Microsatellite instability (MSI) testing is a relatively inexpensive procedure performed on tissue samples from a tumor. Positive results in this test indicate the possibility of LS and the advisability of going forward with genetic testing.

“My personal feeling is that universal testing is a good idea,” Khurana says. “If you look at the current criteria and test for Lynch Syndrome only in people who are under age 50, you are going to miss a significant number of cases. I have been involved in meetings at Vassar Brothers Medical Center to develop criteria that define people whose specimens should be tested with MSI and followed up with genetic testing for them and their family members if results show DNA instability.”

“In our practice at Premier, we pay attention to the red flags that come up in the course of taking a patient’s history,” says Khurana. “If, for example, two or more family members have developed cancer at an early age, I would definitely consider the possibility of Lynch Syndrome and likely advise my patient to undergo genetic testing. Once I’ve explained the reasoning, the benefits and risks, it becomes a personal choice for the patient to make.”

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