Lynch syndrome is a rare disorder also known as hereditary nonpolyposis colorectal cancer (HNPCC) syndrome. Though not a cancer in its own right, Lynch syndrome strongly predisposes people who have this inherited defect to develop colorectal cancer as well as several other types of cancer. The condition is named after Henry Lynch, a doctor and authority on inherited cancers.
Lynch syndrome is caused by mutations or alterations of particular genes. People with Lynch syndrome have more than an 80 percent chance of developing colorectal cancer during their lifetime. Colorectal cancer is relatively common, but only about 3 percent to 4 percent of all colon cancer cases are attributable to Lynch syndrome.
When colorectal cancer is associated with Lynch syndrome, it tends to occur at a younger age than in most other colorectal cancer cases. If your family history suggests that Lynch syndrome may be present, genetic testing can determine if you have Lynch syndrome so that you can consider steps to either prevent the development of colon cancer or at least detect it at an earlier, more treatable, stage.
Although the term "nonpolyposis" appears in the name "hereditary nonpolyposis colorectal cancer," people with Lynch syndrome actually do have polyps, mushroom-like growths of tissue, in the lining of the colon or rectum. However, these polyps tend to be fewer in number compared with the number present in other forms of inherited colorectal cancers such as familial adenomatous polyposis (FAP).
When cancer does occur in people with Lynch syndrome, most cases arise in the right side of the colon. Colorectal cancer associated with Lynch syndrome tends to occur in people at a younger age than for people with the more common nonhereditary forms of colorectal cancer.
In addition to the presence of early polyps, the colorectal cancers associated with Lynch syndrome share many of the same signs and symptoms as other types of colorectal cancer. Although these cancers are often "silent" or symptom-free in their early stages, the following signs and symptoms may be present as the cancer becomes more advanced:
Lynch syndrome runs in families. You can inherit it from either parent in an autosomal dominant inheritance pattern. If you have this condition, there's a 50 percent risk of passing the mutated gene to your children.
The defective gene inherited in Lynch syndrome is responsible for correcting mistakes that may occur when DNA replicates in normal cells. DNA is the genetic material that contains instructions for every chemical process in the body. When our normal cells grow and divide, they must first make a new copy of their entire DNA. It's not uncommon for some minor mistakes to be made during this process, but normal cells have repair mechanisms to recognize when a mistake has been made, and to repair that mistake before a cell divides to form two new cells. However, people who inherit the abnormal gene associated with Lynch syndrome lack the ability to repair these minor mistakes. An accumulation of these mistakes leads to increasing genetic damage within cells and eventually can lead to the cells becoming cancerous.
On average, cases of colorectal cancer associated with Lynch syndrome tend to occur in people younger than age 45, which is about 20 years younger than the more common, nonhereditary forms of colorectal cancer. In people with Lynch syndrome, colorectal cancer can develop early, even in the teens or 20s.
If you have a family history of Lynch syndrome, you're at much greater risk of inheriting this condition yourself. An international panel of doctors and researchers has developed criteria for identifying Lynch syndrome families. These characteristics, called the Amsterdam II criteria, include:
While the Amsterdam criteria give doctors a general idea of which families may pass the genetic mutations associated with Lynch syndrome, the criteria aren't perfect. Many people meet the Amsterdam criteria, but aren't found to have Lynch syndrome. Conversely, many people with Lynch syndrome have families that don't meet the Amsterdam criteria.
Doctors can use other complex criteria to determine your risk of the genetic mutations associated with Lynch syndrome. Often these other criteria take into account more specific information about your cancer, if applicable, and cancers your family members have had. Researchers continue to look for the best way to predict Lynch syndrome risk.
If you have a family history of colorectal cancer — and particularly if your family has characteristics that are part of the Amsterdam criteria for identifying Lynch syndrome families — talk to your doctor about your susceptibility to Lynch syndrome. He or she may recommend genetic counseling or screening to assess your risk.
Having Lynch syndrome not only makes you more susceptible to colorectal cancer, it also increases your risk of other types of cancer. For example, women with Lynch syndrome have a greater likelihood of developing cancer of their ovaries or the lining of their uterus (endometrium). More than one in three women with Lynch syndrome will develop endometrial cancer in her lifetime. Cancers of the stomach, small intestine, urinary tract, liver, prostate, pancreas, brain and skin are also more common in people with Lynch syndrome. If you have Lynch syndrome, talk with a doctor familiar with this disorder, and discuss what screening tests you should undergo to detect any cancer at an early, and more treatable, stage.
Your doctor will take a thorough family history, which is an important step in determining whether you have a risk of inheriting Lynch syndrome. You may also undergo additional diagnostic tests.
Colonoscopy
When doctors suspect the presence of Lynch syndrome with its greater likelihood of developing colorectal cancer, they may recommend a colonoscopy, which is the primary screening test for Lynch syndrome and colorectal cancer.
To prepare for a colonoscopy, you'll be asked to empty your colon completely on the previous day — usually by drinking a special solution, or undergoing one or more enemas, or both. Just before the procedure, you'll take a sedative to minimize or eliminate any discomfort.
During a colonoscopy, a long, thin, flexible tube with a miniature video camera at its tip is threaded through your rectum into the colon, permitting your doctor to view the entire length of the colon on a video display monitor. The monitor allows your doctor to have a clear view of any abnormalities, including noncancerous polyps or tumors. The procedure takes about 15 to 30 minutes. Although side effects such as bleeding or perforation of the colon can occur, they are rare.
According to current American Cancer Society (ACS) guidelines, if you have a family history of Lynch syndrome, be sure to undergo regular colonoscopies beginning at age 21.
If polyps are found during a colonoscopy, your doctor can remove them at the time. Once removed, they are studied in the laboratory to determine if any cancerous or precancerous cells are present. Even when the colonoscopy is normal — and if you either already are known to have Lynch syndrome or your doctor suspects you have the syndrome — your doctor may advise you to repeat this procedure more frequently than the ACS recommendations for the general population. If the results of genetic testing have been positive, or if you haven't undergone genetic testing, schedule a colonoscopy every one to two years until age 40, and then annually. These relatively short intervals between colonoscopies are intended to detect colorectal cancer in its earliest stages when treatment is more likely to be successful.
Tumor testing
In people who may have an inherited predisposition to colon cancer and in whom colorectal tumors have been detected, doctors will order an analysis of samples of tumor cells, often relying on a laboratory test for microsatellite instability (MSI). Microsatellites are sequences of cellular DNA, and in people with Lynch syndrome, there may be errors or "instability" in these sequences. If a colorectal tumor is found to have MSI, additional genetic testing may be necessary to verify that a mutation has occurred in one of the genes associated with Lynch syndrome.
When polyps associated with Lynch syndrome are present, doctors remove them during a colonoscopy. If colorectal cancer is already present, treatment is the same as for other forms of colorectal cancer.
Surgery
When colorectal cancer is detected during a colonoscopy in people with Lynch syndrome, doctors typically advise an operation to make sure all of the cancer has been removed. You should also discuss with your doctor an operation to remove the entire colon (colectomy), but not necessarily the rectum as well.
Surgery may also be an option in people who carry the genetic mutation of Lynch syndrome, even if they don't yet have colorectal cancer. This prophylactic colectomy eliminates the risk of cancer of the colon. Most people with Lynch syndrome choose frequent colonoscopies over prophylactic surgery.
Although colectomies can be performed in a number of ways, a common approach is called total abdominal colectomy with ileorectal anastomosis. This involves the removal of the colon, and then attaching the remaining small bowel to the rectum. Because the rectum remains in place, the person can have normal bowel movements, and thus there is no need for a bag to collect human waste (a colostomy or ileostomy bag).
Other approaches
Additional treatment choices include:
These approaches are often considered supportive treatments, particularly when the cancer has spread beyond the colon wall, with surgery remaining the front-line therapy.
In addition to the regular use of colonoscopy, genetic testing is an important preventive tool. In major medical centers, genetic counselors who specialize in cancer-related mutations can help you determine your risk of Lynch syndrome, and can provide guidance on ways to prevent or detect colorectal cancer at its earliest stages.
These counselors or your doctor may recommend that you and other family members be tested for the presence of genetic mutations. Testing involves drawing a blood sample and sending it to the lab for analysis. When test results are available, a genetic counselor can explain what the findings mean.
Another good approach is to follow the general recommendations of the American Cancer Society for preventing colorectal cancer, which include:
October 30, 2006