This information is about a condition that can run in families called HNPCC (hereditary non-polyposis colorectal cancer). People with HNPCC have an increased risk of developing cancer of the large bowel (colorectal cancer) and some other cancers.

HNPCC is a rare condition that runs in families. Conditions that run in families are known as familial or hereditary. The term non–polyposis differentiates it from another condition called FAP (familial adenomatous polyposis) where hundreds of polyps (small growths) develop in the bowel.

HNPCC is the most common cause of hereditary bowel cancer. Less than 5 in 100 of all bowel cancers are linked to HNPCC.

Women with HNPCC also have an increased risk of developing cancer of the womb (uterus). There is also a slight increase in risk of developing cancer of the ovaries.

People with HNPCC also have an increased risk of stomach, pancreas, biliary and bladder cancers.

Knowing about risk and having regular screening may help prevent some cancers and detect others in the early stages when they’re curable.

HNPCC is sometimes known as Lynch Syndrome after the doctor who discovered it.

HNPCC is caused by a fault in one of the genes known as the ‘mismatch repair’ genes. These particular genes normally work to help prevent you getting cancer.

HNPCC may be suspected in families with close blood relatives who have developed bowel cancer, womb and ovarian cancer over several generations. They may have inherited a faulty copy of one of the mismatch repair genes.

Our genes carry the information that is passed on (inherited) from our parents. They decide things like the colour of our eyes and affect the way our bodies grow, work and look.

Three of the mismatch repair genes (known as MLH1, MSH2 and MSH6) are responsible for most cases of HNPCC. So, if a person inherits a faulty copy of one of these genes, it increases their risk of developing bowel cancer and the other types of cancer we’ve already mentioned.

We have two copies of each gene – one from each of our parents. If someone has HNPCC it means they have a healthy gene but also one that’s faulty.

If that person has a child there is a fifty-fifty chance that they will pass on the faulty gene (only one copy of a gene is passed on from each parent).

HNPCC itself doesn’t cause any symptoms. It’s an inherited syndrome that means a person has a higher risk of developing bowel and womb cancer.

Sometimes the first sign that a person has HNPCC are when the symptoms of bowel or womb cancer develop. This generally happens at a younger age than people whose cancers aren’t inherited and there’s usually a history of these cancers in the family.

Not everyone with HNPCC has a family history of it. This is because some people may be the first in their family to get it.

HNPCC is more likely if there are lots of cases of bowel and womb cancer on one side of your family, and if they were diagnosed at an early age.

Bowel cancer that doesn’t run in families usually develops in people over 50. In HNPCC bowel cancer usually happens between the ages of 40 and 50, or younger.

HNPCC may be suspected if:

• at least two relatives on the same side of the family have had bowel cancer
• a family member developed bowel cancer at a young age (under 45)
• there are cases of bowel and womb cancer on the same side of the family
• three or more relatives on the same side of the family have had one
  HNPCC - type cancer (not necessarily the same kind of cancer).

If you are worried about cancer in your family, speak to your doctor who can refer you to a family cancer clinic.

Being aware of your normal bowel habit is important, particularly if you have or think you may have HNPCC. If you notice any changes or have any of the following symptoms it’s important to get them checked out by a doctor:

• blood on, or in the stools (bowel motion)
• diarrhoea or constipation for no obvious reason (ie a change in the normal bowel habit that lasts longer than six weeks)
• unexplained weight loss
• pain in the tummy or back passage
• a feeling of not having emptied the bowel properly after a bowel motion.

It’s also important to be aware of the symptoms of womb cancer if you have or think you may have HNPCC. Any of the following symptoms should be checked out by a doctor.

• abnormal vaginal bleeding (between periods, heavier periods or bleeding after menopause)
• pain in the lower abdomen (tummy), back or legs
• pain or discomfort during sexual intercourse.

All these symptoms can be caused by conditions other than cancer, but it’s always important to get them checked by your doctor.

It is possible to find out if someone has HNPCC by doing a genetic test. This test is first carried out in someone who has had cancer. If the faulty HNPCC gene is found in that person then close family members (not affected by cancer) can then be tested to see if they have inherited it.

Genetic testing

The test is always carried out first on a member of the family who has developed an HNPCC type of cancer and is willing to have genetic testing. All that’s needed is a blood sample. But it can take a while (up to a year) to get the results as the genes are large and the faulty gene may be difficult to find.

Once the faulty gene has been found other family members can then be tested for the same faulty gene. People always have counselling before any genetic testing is done. This is so that they understand what the results will mean to them.

Sometimes the faulty gene can’t be found in the person with the HNPCC type of cancer (because it’s not HNPCC or there’s a fault in a gene that research hasn’t yet identified). If no gene change is found other family members cannot be tested. However, based on their family history, they can still have regular bowel tests and womb checks (in women) to reduce their cancer risk.

What the test results mean

• If you have already had an HNPCC-type cancer and have the faulty gene, women may then be screened for womb or ovarian cancer.
• If you have HNPCC in your family and have the faulty gene you will be advised to have regular screening to reduce your risk of HNPCC-type cancers.
• If you have HNPCC in your family and have not inherited the faulty gene your cancer risk is the same as anyone else’s. You won’t need screening and your children will not be at an increased risk of HNPCC-type cancers.

Knowing about your risk of cancer means you can have regular tests (screening). Bowel cancers can be picked up early, when they are curable.

If a person is found to have inherited the faulty gene, they will usually be advised to have regular bowel screening from a young age. This may begin at the age of 25, or five years earlier than the age your youngest affected relative developed bowel cancer. Some women may also be offered screening for womb cancer.

If the faulty gene wasn’t found in the person with HNPCC-type cancer, it’s important that you still have screening as you may still be at risk of HNPCC. This is the same if you decided against genetic testing or couldn’t have a test (family member with HNPCC-type cancer didn’t want a test).

Bowel screening

Bowel screening is done with a colonoscopy (test to examine the bowel). During a colonoscopy, a long thin flexible tube is inserted into the back passage to view the inside of the bowel.

A colonoscopy allows any cancers to be diagnosed early on when they are curable. A biopsy (removal of a small piece of tissue) is taken of anything that is suspicious. Any polyps (small growths) can be removed before they develop into a cancer. Colonoscopies are usually repeated every two years.

Colonoscopy

A colonoscopy is usually done in the hospital outpatient department and takes about an hour. Your bowel has to be completely empty for the test. This means you’ll have follow a special diet for a few days before it. On the day before your test you’ll be asked to take medicine (a laxative) to empty your bowel. You will be given instructions about preparing for a colonoscopy by your hospital.

Just before the test, you will be given a drug to help you to feel more relaxed (sedative). This may be given as an injection into a vein (intravenously).

Once you are lying comfortably on your side, the doctor, or nurse, will gently pass a flexible tube (a colonoscope) into your back passage. A colonoscope is a long, thin flexible tube which has a tiny light and a camera on the end of it. It can easily pass around curves so most of the large bowel can be examined. During the test photographs and samples of tissue (biopsies) can be taken.

Afterwards, you will need somebody to go home with you and stay with you for 24 hours until the effects of the sedative wear off. It’s important not to drive during this time.

Womb screening

We don’t yet know if womb screening in women with HNPCC is helpful. Some women may be offered it, but it’s not available everywhere.

The womb can be screened using a procedure called a hysteroscopy or by using vaginal ultrasound. Your doctor or nurse will explain which test you will have.

During a hysteroscopy a thin, flexible tube with a light at the end will be used to look inside the uterus. A vaginal ultrasound scan involves having a small device that makes sound waves, put into the vagina. The sound waves are then converted into a picture by a computer.

Ovarian screening

We don’t know if ovarian screening helps to pick up ovarian cancer at an earlier stage. Occasionally some women may be offered it or they may have it done as part of a research trial. The risk of developing ovarian cancer if you have HNPCC is much lower than your risk of bowel or womb cancer.

Screening can involve a blood test, a vaginal ultrasound, or both. The blood test checks the levels of a protein called CA125.

If you develop bowel cancer, it’s likely to be picked up early through having regular colonoscopies. Any HNPCC-type cancer is treated in the standard way for that type of cancer.

Treatment for bowel cancer will usually involve surgery to remove the cancer. Further treatment with chemotherapy, might be needed depending on the stage of the cancer.

Treatment for womb cancer will usually involve removing the womb (hysterectomy) and the ovaries. Radiotherapy may also be given.

Risk reducing surgery

Occasionally with HNPCC, it’s recommended that the whole of the large bowel is removed as a preventative measure. This is usually only recommended where the risk of developing cancer is thought to be very high, or a person with HNPCC develops more than one bowel cancer.

Some women (when they’ve completed their families) may choose to have their womb and ovaries removed to reduce their risk of womb and ovarian cancer.

Knowing that you have HNPCC, or are at risk of it, can be very difficult to cope with. The uncertainty of not knowing if you will develop cancer isn’t easy to deal with, but it’s important to remember that bowel cancer can be found early and cured. You may have concerns about genetic testing, screening or whether you should have risk reducing surgery. It’s important to talk these concerns over with the doctors and nurses caring for you. They’ll be happy to answer any questions you have.

You may have many different emotions including anxiety and fear. These are all normal reactions, and are part of the process that many people go through in trying to come to terms with their condition. Many people find it helpful to talk things over with their doctor or nurse. Close friends and family members can also offer support.

This section has been compiled using information from a number of reliable sources, including:

• Risk Assessment and Management in Cancer Genetics. Lalloo F, B Kerr, J Friedman, D G Evans. Oxford University Press, 2005
• What is HNPCC? Genetic Health www.genetichealth.com (April 2007)

For further references, please see general bibliography.