Hereditary Non-polyposis Colorectal Cancer (HNPCC)

HNPCC is an inherited genetic mutation that causes to develop colon, rectal  or bowel cancer.

In people with HNPCC, bowel cancer typically develops at a younger age than non-hereditary bowel cancer – around the ages of 40 to 50 rather than 60 to 70.

Some of the genes (basic units of heredity) that cause HNPCC are known. Nonpolyposis means that colorectal cancer can occur when only a small number of polyps is present (or polyps are not present at all). In HNPCC, colorectal cancer occurs primarily on the right side of the colon (you may see the  diagram). Sometimes other cancers can occur in families with HNPCC. They include cancer of the uterus, ovary, stomach, urinary tract, small bowel, and bile ducts. Other names for HNPCC are Lynch syndrome and cancer family syndrome.

The gastrointestinal digestive tract is a hollow tube which begins at the mouth and ends at the anus. It has several parts including the esophagus, stomach, small intestine and colon (large intestine). Its total length is about 28 feet. The last 5-6 feet of the intestine is called the colon (large intestine, large bowel). The last 5 or 6 inches of the colon is the rectum. After food is digested, solid wastes move through the colon and rectum to the anus, where they are passed out of the body.

What are Polyps: Polyps are abnormal, mushroom-like growths. When found in the gastrointestinal tract, they occur most commonly inside the colon (large intestine, large bowel). Polyps vary in size from less than one-tenth of an inch to 1-2 inches. They may be so large as to block part of the intestine. In some people polyps may be inherited, while in others they are not inherited. Certain types of polyps can turn into colon cancer or rectal cancer.

HNPCC is also called Lynch syndrome. Henry T. Lynch (professor of medicine at Creighton University Medical Center), characterized the syndrome in 1966. In his earlier work, he described the disease entity as “cancer family syndrome.” The term “Lynch syndrome” was coined in 1984 by other authors, and Lynch himself coined the term HNPCC in 1985. Since then, the two terms have being used interchangeably, until more recent advances in the understanding of the genetics of the disease led to the term HNPCC falling out of favor.

How HNPCC is inherited: People with HNPCC have a 50% chance of passing the HNPCC gene to each of their children (see diagram p. 5). The gene can be passed on even if the parent has had surgery to remove his or her own colon. Individuals who do not inherit the gene cannot pass it to their own children. The vast majority of individuals with HNPCC develop cancer.
Some individuals with HNPCC do not have an affected parent. These individuals, who are the first to have the condition, are referred to as having a new mutation (newly altered gene). They can, however, pass this HNPCC gene to their children.
In the United States, about 160,000 new cases of colorectal cancer are diagnosed each year. Hereditary nonpolyposis colorectal cancer is responsible for approximately 2 percent to 7 percent of all diagnosed cases of colorectal cancer. The average age of diagnosis of cancer in patients with this syndrome is 44 years old, as compared to 64 years old in people without the syndrome.

Symptoms include a change in bowel habit (needing to visit the toilet more frequently, with diarrhoea or constipation), the passage of blood with faeces, weight loss(Unusual and continuing lack of energy), change in appetite, abdominal pain and even an abdominal mass.

It should be emphasized that there is no safety in simply waiting for symptoms to develop. It is vital that persons at risk make every effort to have examinations starting by age 25 or 5 to 10 years before the age of the earliest colorectal cancer diagnosed in the family, even if they do not have symptoms.
Causes and risk factors:-
The genes affected are known as repair genes, which means they normally detect and repair damage in DNA that occurs when DNA is copied during cell division. However, when the genetic mutations are present, mistakes in DNA persist. The faulty DNA accumulates leading to uncontrolled cell growth and hence a risk of cancer.

The genes associated with HNPCC can sometimes cause other cancers, such as stomach, small intestine, liver, gall-bladder, ovary, endometrium (the lining of the womb), kidney, brain, skin and prostate gland.

Diagnosis: –
Persons at risk for HNPCC usually have a family history of two successive generations of colon cancer or at least one generation with colon cancer and one generation with polyps. Men and women at risk for HNPCC need examinations of the entire colon. Women at risk should also have yearly endometrial screening. Two tests, colonoscopy and barium enema, are available to tell whether polyps or cancer is present in the colon. For patients at risk for HNPCC, colonoscopy is the preferred method of screening.

1.Colonoscopy is an examination by means of a flexible, lighted tube, slightly larger in diameter than an enema tube, that is inserted into the colon. Tiny amounts of tissue may be removed from any part of the colon for microscopic study during this procedure. Before a person undergoes a colonoscopy a sedative is given; many persons sleep through the whole procedure and feel little or no discomfort. During this procedure it is sometimes necessary for the doctor to insert some air into the colon. Occasionally, air will cause the same kind of discomfort as a gas pain.

2.Barium enema is a test in which a white liquid called barium is inserted as an enema into the colon. This test allows the colon to be outlined when an x-ray picture is taken. If polyps are present they can be seen on the x-ray. The barium enema feels much like an ordinary enema, causing a feeling of fullness. This test should not be performed on pregnant women because of the risk of x-rays to the fetus.

For both of these tests of the colon, the patient must undergo a preparation before examination. The preparation, which includes a liquid diet and laxatives, clears stool from the colon so that all areas of the colon can be inspected. Exact instructions will be provided by the doctor before the examination.

A blood test for the HNPCC gene will tell at-risk family members if they have inherited the gene mutation identified in the family. However, gene tests do not reveal the presence of polyps or cancer.

If a polyp is found, removal through the colonoscope may be sufficient, although surgery may be recommended for some patients. If cancer is found at examination, the doctor will recommend colon surgery. Removing the entire colon is the only way to completely prevent the development of colon cancer or to treat existing cancer.

Several different operations are currently available for treatment of HNPCC. The three most commonly performed operations are total colectomy with: 1) ileorectal anastomosis, 2) ileoanal pull-through (pouch procedure), or 3) ileostomy. All three operations involve removal of all or most of the colon. After a complete discussion of these operations, the patient and surgeon together can decide which one is best. Women with HNPCC may also consider surgical removal of the uterus, ovaries, and Fallopian tubes.

In some cases, after colon removal, a person may have an ileostomy. An ileostomy is an opening on the abdomen through which stool leaves the body An ileostomy can be temporary or permanent. In most cases it is necessary to wear an appliance called an ileostomy bag to collect body wastes.

An ileostomy should not be considered a handicap, although it is an inconvenience. With proper care, there should be no odor or uncleanliness. Thousands of people of every age and of both sexes have had ileostomy surgery. After surgery, people can be just as busy, successful, and involved in daily routines as before surgery; in fact, they may be more active because of improved health.

However, someone with the abnormal genes can be screened for tumours.

However, someone known to have an abnormal HNPCC gene (or others in the family) can be screened for tumours with regular colonoscopy, gastroscopy and hysteroscopy, so problems may be caught much earlier when treatment is more likely to be effective.

Seven genes have been identified as causing the majority of cases of HNPCC: MSH2, MLH1, PMS1, PMS2, MSH6, TGFBR2 and MLH3. Blood tests may be used to detect them. These genes for HNPCC are inherited in an autosomal dominant pattern, which means that a person has a 50% chance of passing the abnormal gene on to each of their children. However this doesn’t mean a 50% chance of cancer in the child as not all those who inherit the genetic mutation will go on to develop cancer.

Antenatal screening is not usually offered.

Follow up  care after surgery:-
Early diagnosis of HNPCC in many patients has led to early surgery, resulting in prevention or cure of colon cancer and increased life span. However, other complications of this hereditary condition may still occur. For example, individuals with HNPCC appear to be at an increased risk for cancer of the endometrium (uterus), ovary, stomach, urinary tract, small bowel, and bile ducts. If you have had surgery for HNPCC, follow the guidelines below.

Exam guidlines for people with HNPCC aand who have had surgery:
1.Sigmoidoscopy every year (depending on type of surgery).

2.Annual hemoccult test.

3.Annual physical exam.

4.For women: annual gynecological exam, including endometrial screening with biopsy (consider vacuum curettage or Pipel biopsy).



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