FAQ: Familial risk of pancreatic cancer
Question: Does pancreatic cancer run in
families?
Answer by Professor John P Neoptolemos MA, MB, BChir,
MD, FRCS
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
What Are Genes?
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.
Which Genes Are Involved In Pancreas Cancers?
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 (VHL)
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).
Special Follow Up Of Patients With An Inherited Pancreas Cancer
Risk
General Screening For Cancer
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).
Genetic Testing in Familial pancreatic Cancer
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).
Screening In Patients With MEN-1
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.
Screening In Patients With VHL
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.
EUROPAC
European Register for Familial Pancreas Cancer and Hereditary
Pancreatitis. The principal register in Europe providing advice and
research in inherited pancreatic disorders.
How taking part in the EUROPAC project will help in the
treatment of pancreatic cancer.
Half the people in a pancreatic cancer family will not have the
gene that would predispose them to cancer, these people are in no
greater risk of pancreatic cancer than any other person in the
general population. For those people at risk the best course of
action would be regular screening with the best technology
available, but this is unnecessary for all those family members who
are not carrying the gene. The problem is that in most cases we do
not know what the gene is. To identify the gene we need blood
samples from patients with cancer and (equally important) family
members without cancer. This has already allowed us to identify the
role of BRCA2 in some of our families, we are closing in on other
genes. An added advantage of finding these novel genes will be that
in this way we will learn more about the causes of the disease and
this will help in the development of new therapies for pancreatic
cancer. Also the ability to identify high risk patients will allow
us to develop, test and perfect novel screening systems to detect
early pancreatic cancer.
Write to:
EUROPAC Co-ordinator
Division of Surgery and Oncology
Royal Liverpool University Hospital
Daulby Street
Liverpool, L69 3GA.
europac@liv.ac.uk
www.europac-org.eu
Article by:
Professor John P Neoptolemos MA, MB, BChir , MD, DRCS
Professor of Surgery and Head of Division of Surgery and Oncology
University of Liverpool and Honorary Consultant Surgeon, Royal
Liverpool University Hospital
Division of Surgery and Oncology University of Liverpool
5th Floor, UCD Block Daulby Street
Liverpool
L69 3GA