What is Hereditary Non-polyposis Colorectal Cancer?
HNPCC is an inherited colorectal cancer syndrome and accounts for 5 percent of all cases of colorectal cancer. The “H” stands for hereditary, meaning it is inherited or can be passed from parent to child; “N” stands for non-polyposis, contrasting it to the inherited condition FAP where hundreds to thousands of polyps develop in the colon; “CC” stands for colorectal cancer, the most frequent cancer that develops in these families. Patients with HNPCC have an 80 percent chance of developing colorectal cancer.

The cause for HNPCC is due to an inherited mutation (abnormality) in a gene that normally repairs our body’s DNA. There are at least 5 genes that have been found to cause HNPCC. They are called Mismatch Repair Genes. If part of the DNA is not matched properly cancer can occur. Because the HNPCC gene mutation is present in every cell in the body’s other organs can develop cancers too. Cancer of the uterus (womb or endometrium) is very common and may be the main cancer in some HNPCC families. Other cancers can occur in the rest of gastrointestinal tract (stomach, small intestine, pancreas), urinary system (kidney, ureter) and female reproductive organs (ovary). Although the risk to develop cancer in HNPCC is high, knowing about the risk of cancer and getting appropriate check-ups and treatment by experts in this disorder can save lives and prevent cancer.

How is HNPCC diagnosed? Family History The first step in suspecting someone belongs to an HNPCC family is by reviewing the family history. The most strict definition of an HNPCC family is called the Amsterdam criteria. It includes: • 3 relatives with colorectal cancer (one first degree relative to the other two) • 2 successive generations • 1 colorectal cancer occurring in someone 50 years old or less The colon cancers are often found in the right colon and usually occur before the age of 50.

Other clues to an HNPCC family include multiple relatives with colon cancers, including relatives who have had more than one colorectal cancer, or a colon and endometrial cancer, and clusters of colorectal and other cancers of the gastrointestinal, urinary or female reproductive system.

Genetic testing
A significant breakthrough in the diagnosis of HNPCC was made with the discovery of the genes that cause HNPCC. These genes are called Mismatch Repair Genes. Mismatch repair genes find pieces of DNA that are not matched together properly and repair the mismatch. If a mutation occurs in one of the known mismatch repair genes, DNA becomes abnormal and predisposes all of the body’s cells to cancer. Blood testing for these genes in now available. It should be done on someone that has had an HNPCC cancer first. If the gene mutation for HNPCC is detected in that person other family members can be tested. Approximately 50% of HNPCC families have a mutation detected. An alternative method for identifying people who may have inherited the gene mutation for HNPCC includes a test on colon tissue called microsatellite instability (MSI). This test is only supportive evidence that someone may have HNPCC. Direct DNA sequencing should be done if MSI is present in tissue. Gene tests only detect who has or has not inherited the abnormal gene. It does not detect polyps and cancer. If the families gene mutation cannot be found, or if someone does inherit the family mutation for HNPCC, regular check-ups are essential to prevent cancer or detecting it early in the curable stages.

Colon examinations
Through regular colorectal checks polyps can be removed before they turn into cancer or cancer can be detected early when still curable. Examinations of the colon are the only way to detect colon polyps or colon cancer. There are two main ways to examine the colon. One is by an x-ray test called a barium enema. This examination may not pick up small polyps and cancers and is not recommended for patients with HNPCC.

The best test to examine the colon in patients with HNPCC is through a test called a colonoscopy. The shorter instrument that examines the lower one third of the colon, called a flexible sigmoidoscopy, should not be used. The colon cancers are often found in the right colon and cannot be detected with the sigmoidoscope. A colonoscope is a thin, flexible tube that is passed into the colon. It has a light on the end and allows the doctor to examine the lining of all 6 feet of the colon. In addition, instruments can be passed through the scope to sample or remove polyps. Patients drink a special solution to cleanse the colon the night before the test. The doctor usually gives a sedative through the vein just before inserting the scope. The exam of the entire 6 feet of the colon takes about 20 minutes and is usually quite comfortable. Patients cannot drive for about 8 hours after the procedure because of the effects of the sedative. Someone must drive the patient home but light duties can be resumed the rest of the day. If colorectal cancer or polyps occur in the right colon or at an early age the likelihood that someone has HNPCC is very high.

What is the treatment for HNPCC?
Surgical removal of the entire colon is the only definite way to prevent colon cancer. Removal of an organ before cancer occurs is called prophylaxis. Prophylactic colectomy (removal of the colon) or hysterectomy (removal of the endometrium and ovaries) is controversial and should be discussed with experts caring for patients with HNPCC.

If a polyp is found it can most often be removed through the colonoscope. Occassionally, surgery may be recommended if the polyp is large or as prophylaxis once polyps are detected.

If colorectal cancer is found surgery to remove the entire colon is necessary. That is because of the high risk of getting additional colon cancers. There are a variety of operations available. Depending on the expertise of the surgeon, any of the following operations can be performed through small holes in the abdomen called laparoscopy or through the standard abdominal incision called laparotomy.

The options include:

Total colectomy and ileorectal anastamosis (IRA) During the operation, the surgeon removes the patient’s colon but leaves 5 inches of the rectum. The small intestine, or ileum, is then surgically joined to the upper rectum. Afterwards, the patient has normal bowel function.

Colectomy with ileoanal pouch (Restorative proctocolectomy) This surgical procedure is successful in selected patients. The surgeon removes the colon and the rectum, leaving the anal canal and the anal sphincter muscles. A new rectum is made from the small intestine and attached to the anal canal. Sometimes a temporary opening in the abdomen, called and ileostomy or stoma, is created. After the first operation has healed, the ileostomy is closed, restoring normal bowel function.

Proctocolectomy and ileostomy This procedure is recommended for patients with rectal cancer or who cannot have the other operations. Both the colon and rectum are removed, and a permanent ileostomy is created. Patients then wear a bag to collect wastes that leave the body through the ileostomy.

How long is the hospital stay?
The length of stay in the hospital depends on the type of surgery performed. The usual stay is less than one week.

What about recovery?
After hospital discharge, recuperation at home is four to six weeks. Patients usually return to work or school in six to eight weeks. Your doctor will discuss this with you at your post-operative visit four to six weeks after surgery.

What lifestyle changes can be expected?
Most patients are able to eat normal diets and lead normal lives following surgery. Some people notice more frequent bowel movements. Otherwise, their lives will be perfectly normal. Their sexual and social activities are unaffected. None of the procedures affects a man’s ability to father children nor a woman’s ability to have a normal pregnancy. However, the way in which a baby is delivered may be affected by the type of surgery and should be discussed with the surgeon.

What testing is needed to keep patients with HNPCC or at risk of HNPCC healthy?

Prevention Through Participation in a Registry

The Importance of the Registries
The Inherited Colorectal Cancer Registries (ICCR) at the Cleveland Clinic have one main purpose: to prevent needless deaths from colon cancer.

To reach this goal, the registries staff tires to make sure that patients receive early diagnosis and treatment. The registries accomplish this by screening family members of patients who may be at risk for colorectal cancer. The staff also ensures that patients diagnosed with the disease are aware of the necessary screenings and follow-up visits to their physicians.

Because colorectal cancer and polyps have such a strong hereditary link, keeping track of patients and their family members through a registry saves lives.

Referrals to the registry vary. Patients often make their own appointments. A community physician may send a patient to one of the Clinic’s colorectal physicians, or a patient may hear about the registries from other family members who are Clinic patients.

A registries team member will then ask that patient a series of questions about his or her family, in particular which family members have developed polyps or colorectal cancer. With the answers to those questions, the registries coordinator will determine that patient’s family history and construct a family tree. This family tree can help determine other family members’ risk for developing colon cancer.

There are many advantages to being included in the registries. Patients and their family members will receive annual screening letters, booklets and newsletters. The registries team can also answer questions, make appointments, and share new research developments and results from clinical trials with patients and families in the registries.