The European registry of familial pancreatic cancer and hereditary pancreatitis

Plain English Summary

Background and study aims
Pancreatic cancer is the tenth most common cancer in the UK with around 10,000 people diagnosed each year. Pancreatic cancer has the lowest survival of all common cancers, with less than 1 in 4 surviving more than 1 year after diagnosis and less than 1 in 14 surviving beyond 5 years. In most cases, we do not know why pancreatic cancer develops, but we do know of risk factors that increase the likelihood of developing the condition. These factors include age, tobacco use, obesity and genetic factors. Having any one, or a combination of these does not mean you will definitely develop cancer.
Pancreatic cancer is a difficult cancer to diagnose, with less than 1 in 5 people being diagnosed at an early stage when treatment is most likely to be successful. Unfortunately, only 1 in every 10 people with pancreatic cancer will receive potentially curative surgery, only 2 in 10 will receive chemotherapy and 7 in 10 will not receive any active treatment. Nearly half of pancreatic cancer cases are diagnosed through an emergency presentation, where the one-year survival rate is only 12% which is three times lower than people diagnosed through a GP referral.
Most cases of pancreatic cancer appear out of the blue, with no previous family history of the condition. There are, however, families where there is more than one case of pancreatic cancer. This could be entirely coincidental but, in some cases, pancreatic cancer develops in these families because of a faulty gene that is inherited by affected individuals (familial pancreatic cancer).
Every organ in your body is made up of millions of cells. The growth of these cells is normally very carefully controlled; cancer develops when these cells grow out of control, forming a lump. Cell growth is controlled by the genes within each cell and damage to these genes can result in loss of control of how your cells divide. In many cancers, we know which genes have been damaged to cause that specific cancer, but in the majority of families with a history of pancreatic cancer, we do not yet know the causative gene.
Through years of dedicated research into pancreatic cancer, we now know some of the genes that cause pancreatic cancer to develop, however, we are still a long way from fully understanding the genetic cause of inherited pancreatic cancer.
We want to further our understanding of the genetic cause of pancreatic cancer. We want to understand the role of known genes in the development of pancreatic cancer and also want to search for other genetic causes of pancreatic cancer that have not yet been discovered.

Who can participate?
Registry:
1. Two first-degree relatives with pancreatic adenocarcinoma.
2. A family with three or more relatives with pancreatic ductal adenocarcinoma.
3. Families with pancreatic cancer and other cancers (e.g. bowel, breast/ovarian, melanoma, gastric) that suggest a known cancer predisposition syndrome.
4. Families with a known inherited cancer syndrome (e.g. Hereditary Non-Polyposis Colorectal Cancer (HNPCC), familial atypical multiple mole melanoma (FAMMM), Lynch syndrome) with one individual affected by pancreatic cancer
5. Peutz-Jeghers syndrome
6. Families with a causative gene linked to pancreatic cancer (e.g. BRCA2 or yet undiscovered genes) and at least one case of pancreatic cancer in the family
7. Families with two or more relatives with idiopathic pancreatitis
8. Families with at least one case of pancreatitis and a confirmed causative mutation in the PRSS1 gene

Screening:
1. Individuals over 40 years of age from an established pancreatic cancer family. Inheritance of predisposition consistent with high penetrant autosomal dominant inheritance. For example, at least two first-degree relatives with pancreatic ductal adenocarcinoma, where no non-penetrant carriers have to be assumed over the age of 75 years
2. Unaffected member of a family with an associated cancer syndrome and at least one case of pancreatic cancer, who has been shown to carry the relevant genetic alteration
3. Any member of a hereditary pancreatitis family who has been confirmed to carry a causative PRSS1 mutation
4. An affected member of a family consistent with HP who has tested negative for known causative PRSS1 mutations
5. Individuals incidentally found to have cystic lesions or other clinical features that indicate an increased risk of pancreatic cancer may also be included
6. There will be adaptation to risk models as the study progresses to fit the needs of the study outcomes as the study progresses

What does the study involve?
Registry:
Should you wish to register your family details with EUROPAC, we need you to complete a questionnaire that will give us all the information we require to enter your family into our database. The questionnaire is all about you, your lifestyle and relevant medical history and asks about all of your relatives, whether they are alive or not, any relevant medical history and the cause of death of any deceased relatives.
We want the information we put in our database and any advice that we give to you and your family, to be as accurate as it possibly can. We will not proceed with your registration unless we have all the necessary information that we need to do so. The most important part of this process is to confirm the information you are giving us about your affected relatives. We require confirmation of diagnosis for any relative who has been affected by pancreatic cancer or who has a relevant genetic syndrome. We can only accept confirmation in the form of:
1. A letter from a pancreatic specialist, clinical geneticist or GP with all of your relative’s details stating the diagnosis of pancreatic cancer or a relevant genetic syndrome.
2. A death certificate stating pancreatic cancer as the cause of death

Screening:
Everyone who is offered the opportunity to take part in the screening will be seen in our EUROPAC clinic at the Royal Liverpool Hospital or offered a telephone appointment. At this appointment, we will discuss your personal and family history again and talk through the rationale and process of screening. You will have the opportunity to ask any questions and we will confirm your intention to take part and sign a consent form.
We work with a number of collaborators across the UK who can facilitate screening. If appropriate, we can refer you to a local screening centre who will offer you an appointment to meet them before screening.
After your clinic appointment, we will start the screening process. This will involve blood tests and scans of your pancreas that will be performed either: every 6 months, annually, or every other year, depending on your risk. A set of baseline investigations will be arranged. Analysis of your pancreatic juice may be available. You can choose to take up any or all the options. Once the results of your investigations are available, we will write to you with the outcome and inform you of any further action that may be required.
You will either be seen in clinic, or contacted every year. At this annual check-in, we will check for any changes in your medical history, or if there have been any new developments in your family. We will talk through the results of your screening investigations and confirm with you your willingness to continue the screening process.
The blood tests and imaging can all be described as the best medical management for high-risk patients. The collection of pancreatic juice for molecular analysis is a research investigation. The findings are convincing within a laboratory setting but the molecular analysis has not been proven in living subjects in an ongoing trial.
No aspect of normal medical treatment will be withheld as part of this trial and at the end of the trial, it is expected that the results will be published in the scientific literature. You would not be identifiable to others as a result of any publications.

What are the possible benefits and risks of participating?
Registration:
We recognise that this can be a worrying process to go through. Hearing that you or members of your family are at increased risk of developing illnesses like pancreatic cancer can be worrying. If you or any of your family members are struggling to process the information provided as a result of registering with us, please contact the EUROPAC office and we can arrange to talk through this with you. However, as we are not able to formally provide specific genetic counselling, we may also suggest talking to your GP or a clinical geneticist for further information.
Taking a blood sample from you should be a straightforward process and not affect you in any way. Occasionally, superficial bruising can occur around the area where the sample has been obtained. If an attempt to take blood from you is unsuccessful, this will not impact your registration with EUROPAC.
Genetic testing can reveal altered genes that can predict your susceptibility to certain illnesses in the future. We will only disclose the results of genetic tests that may be relevant to the family to participants who request us to do so.
Although every effort is made to preserve your confidentiality and protect your anonymity, it is theoretically possible for collaborators to identify you from information shared with them.

Screening:
All the screening methods have advantages and disadvantages.
The blood tests are very low risk, and a serious complication would be very rare. All the equipment used will be sterile, single-use equipment in common use within the NHS. A bruise would be a relatively common complication.
The CT scan builds up an image by passing radiation through the body. It is known that moderate and high doses of radiation are damaging and, at worst, could even cause cancer. The risk of cancer from each CT scan is described as low and calculated at somewhere between a one in a thousand and one in ten thousand chance. A single CT scan of the abdomen has been calculated to be the equivalent of a few years of normal background radiation. For this reason, we only conduct one baseline CT scan.
The MRI scan uses strong magnets to generate the images. If you have any metallic implants in your body (such as coils in the blood vessels around your brain or a pacemaker), it is very unlikely that you will be able to have an MRI. We will talk about this in the clinic. You will lie on a bed and pass through a tunnel during the scan, if you have claustrophobia or become anxious in enclosed spaces you may not tolerate the MRI.
The EUS involves the insertion of a scope through the mouth, down your food pipe (oesophagus) and into the stomach, where images of the pancreas are obtained by a very high-definition ultrasound. The throat is numbed with local anaesthetic and you are sedated during the procedure so it is normally well tolerated. There is a risk of causing damage to the gullet or stomach during the procedure. This is a rare complication (and can very rarely be fatal) that occurs at a rate of between one in a thousand and one in ten thousand procedures. If this were to occur, it can be treated and may (but doesn’t always) require an operation to repair it.
The OGD and collection of the duodenal juice aspirate carries a similar risk of puncturing an organ as the EUS described above and is otherwise a similar procedure.
You may find that having screening investigations makes you more anxious about your health and your cancer risk. This is difficult to predict. Other people find having the investigations reassuring as it helps to put their minds at rest.
Any of the blood and imaging methods could detect a problem that is unrelated to pancreatic cancer. CT scans are very effective at detecting problems within the body and there is always the possibility of finding something unexpected. If this falls within the expertise of the clinician who would oversee the screening process for you, they would deal with this. If appropriate, you would be referred to another specialist. Conversely, all the investigations performed are targeted towards your pancreas so there is a small chance that conditions developing outside of your pancreas may not be detected as this is beyond the scope of the imaging being performed.
It is possible that the screening investigations could detect a problem with the pancreas. Growths can be “benign”, (for example, inflammation or scarring) or could be a cancer. It is difficult to tell the difference between the two without performing further investigations. This may include further scans or biopsies of an area of concern. If a growth is found and it is possible to remove it, your consultant would discuss your options with you in the clinic and an operation may be offered.

Where is the study run from?
The University of Liverpool (UK)

When is the study starting and how long is it expected to run for?
July 2019 to July 2039

Who is funding the study?
1. NHS England
2. Pancreatic Cancer UK
3. Cheshire and Merseyside Cancer Alliance

Who is the main contact?
Study Coordinator, europac@liverpool.ac.uk

Study website

Contact information

Study information

Eligibility

Locations

Countries of recruitment

• England
• Northern Ireland
• Scotland
• United Kingdom
• Wales

Study participating centres

Sponsor information

University of Liverpool
University/education

Clinical Directorate
University of Liverpool
4th Floor Thompson Yates Building
Liverpool
L3 5RB
England
United Kingdom

Phone	+44 (0)151 795 1256
Email	sponsor@liverpool.ac.uk
Website	https://www.liverpool.ac.uk/
"ROR"	https://ror.org/04xs57h96

Funders

Funder type

Government

Results and Publications

Study outputs

Editorial Notes

04/04/2025: Publication reference added.
24/01/2025: Study's existence confirmed by the University of Liverpool.