Does Pancreatic Cancer Run In Families?

In general, the answer is NO. Nevertheless in rare cases there are families in which pancreatic cancer can run in families. These include the following.

• Families with familial cancer syndromes including Peutz-Jeghers Syndrome, Breast and Ovarian Cancer Syndromes, Familial Atypical Mole and Melanoma Syndrome and Familial Adenomatous Polyposis.
• Hereditary Pancreatitis.
• Familial Pancreatic Cancer.
• Hereditary Pancreatic Neuroendocrine Tumours including multiple endocrine neoplasia type 1 (MEN-1) and von Hippel-Lindau disease (VHL), neurofibromatosis type 1 and tuberous sclerosis.

Inherited pancreas cancer happens because there is an altered gene that predisposes to cancer and is passed on from one generation to the other.

Each person has exactly the same number of genes as every other person. The total number of genes is about 30,000. Genes are in the nucleus of each cell of the body. Genes are like the blueprints in a factory. These blueprints (or genes) enable the cell to make proteins which then organise the two other types of basic molecule (carbohydrates and fats) to create particular types of cell and hence the different organs (such as liver, arms and legs and so on).

In the cells of different organs only some of the 30,000 genes in the nucleus are selected for use. This number varies from 6,000 to 10,000 genes in any particular cell. The different combination of genes used as blueprints for making proteins is how the human body can be organised in such a complicated way (compared to a simple worm that has only 900 genes).

Genes are always in pairs, so that one set comes from the mother and one set comes from the father. There are tiny variations in each gene. These tiny variations are essential to make every person an individual. Occasionally a tiny variation in a gene can give rise to a disease condition. An alteration in a gene that gives rise to a disease is often referred to as a mutation (this is a Latin word that simply means 'changed'). Patients and their families with an inherited cancer risk require the care of a specialist surgeon, paediatrician or gastroenterologist and genetic counselling.

• The main genes involved in all of the major familial cancer syndromes are known. The names of the genes sound quite strange so we only tend to use the short version name of each gene. The gene for Peutz-Jeghers Syndrome is the STK11 gene, the genes for Breast and Ovarian Cancer Syndromes are BRCA1 and BRCA2, the gene for Familial Atypical Mole and Melanoma Syndrome is the p16 gene and the gene for Familial Adenomatous Polyposis is the APC gene.
• The main gene for Hereditary Pancreatitis is the PRSS1 gene.
• The main gene for Familial Pancreatic Cancer is not known, although 10-20% of families have a BRCA2 gene mutation.
• The gene for multiple endocrine neoplasia type 1 is the MEN-1 gene.
• The gene for von Hippel-Lindau disease is the VHL gene.
• The gene for neurofibromatosis type 1 is NF-1.
• The genes for tuberous sclerosis are the TSC-1 and TSC-2 genes.

Multiple Endocrine Neoplasia Type 1 (MEN-1)

This is an autosomal dominant familial cancer syndrome (passed on by the mother or the father) with tumours in small glands in the neck (called parathyroids), a small gland attached to the brain (called the anterior pituitary) as well as the pancreas. The neuroendocrine tumours in the pancreas are usually multiple.

Von Hippel-Lindau disease is another type of rare autosomal dominant familial cancer syndrome (passed on by the mother or the father). This condition causes a multiplication of small blood vessels in the brain, spinal chord and back of the eyes and also cancers of the kidney and the small gland next to the kidney called the adrenal gland. About two thirds of patients with VHL also have a problem with the pancreas, but this is usually in the form of simple harmless cysts. About one in ten people with VHL however will also have one or more pancreatic neuroendocrine tumours (these are usually non-functioning).

Patients from families with familial cancer syndromes (including Peutz-Jeghers Syndrome, Breast and Ovarian Cancer Syndromes, Familial Atypical Mole and Melanoma Syndrome and Familial Adenomatous Polyposis), Hereditary Pancreatitis and Familial Pancreatic Cancer will need to undergo regular screening for cancer. Screening for cancer in high risk individuals is known as secondary cancer screening. The International Association of Pancreatology recommends that all patients be seen at a special pancreas centre. There is no standard set of methods at the present time and the following are only suggestions based on current practice in major pancreas cancer screening centres.

• In principle screening should start at the age of 40 years or ten years earlier than the youngest affected family member.
• All patients should have a baseline endoscopic ultrasound (EUS) and computerised tomography (CT) scan along with a tumour marker (such as CA 19-9). A magnetic resonance imaging (MRI) scan is an alternative to a CT scan but an abdominal ultrasound scan is not acceptable.
• After this, the EUS and blood tests should be repeated every year.
• The CT scan or MRI scan can be repeated every three years, depending on EUS appearances.
• In the case of Hereditary Pancreatitis the pancreas may be so damaged as to invalidate the EUS, in which case CT or MRI are recommended annually.
• If possible participate in a research programme such as EUROPAC and provide pancreatic juice samples for experimental molecular testing every 1-3 years (see below for contact details).

• These families should undergo general secondary screening for cancer as above.
• A proportion of families with Familial Pancreatic Cancer will have a mutation of the BRAC2 gene. Individuals from these families must be referred for genetic counselling and BRCA2 gene testing.
• The families should also be invited to join the European programme searching for the main Familial Pancreatic Cancer gene (includes EUROPAC, see below for contact details).

Surveillance of carriers of the MEN-1 gene should begin in early childhood with blood tests every year and imaging every 3 years. Consensus guidelines have recommended screening from the age of 5 years for anterior pituitary tumours with blood tests (called prolactin and insulin like growth factor-1) and MRI and for insulinoma also MRI along with blood tests (called fasting glucose and insulin). Screening for parathyroid tumours should begin from the age of 8 years with blood tests (called calcium and parathyroid hormone) and for chest and abdominal tumours from the age of 20 years by CT. Other neuroendocrine tumours should also be screened from the age of 20 years using other blood tests (called chromogranin A, glucagon and proinsulin) and MRI, CT or octreotide scan. There should also be endoscopy for gastric tumours (carcinoids) and EUS for duodenal and pancreatic tumours.

Surveillance of carriers of the VHL gene should begin at the age of 10yrs initially with abdominal ultrasound repeated annually looking to find tumours in the kidneys, adrenal glands and pancreas gland as well as the pelvis. From the age of 20yrs there should be 1-2 yearly abdominal CT or MRI scans. For the pancreas again EUS examinations are to be preferred.