Genetic Cancer Prediction through Population Screening (GCaPPS) - Lay Version

What is GCaPPS?

GCaPPS is a research study evaluating the feasibility of offering genetic testing to everybody in the population. The aim of this genetic test (a straight-forward blood test) is to identify individuals at high risk of developing cancers linked to certain inherited gene alterations.

Background information

Genes are basic units of inheritance. They contain the blueprint of all hereditary information. Our genes are made up of building blocks called DNA. Each gene is a short sequence of DNA which corresponds to a unique set of instructions. These instructions are responsible for the characteristics of an individual. Some individuals may have an alteration in their DNA sequence or genetic code. This is called a mutation. Those who carry an alteration in certain genes are at a greater risk of developing cancer. Two such genes are known as the BRCA1 and BRCA2 genes (pronounced “brakka-1” and “brakka-2”). Individuals carrying an alteration in the BRCA1 and BRCA2 genes have a high risk of developing breast, ovarian and prostate cancer. Each of their children (irrespective of sex) has a 50%, or 1 in 2 chance, of inheriting the altered gene. Established early detection and preventive strategies such as screening and surgery are available to manage the cancer risk of these ‘at risk’ individuals. Individuals carrying an altered gene may be identified through genetic testing. This involves a straight forward blood test just like any other blood test. At present this test is only available (on the NHS) to individuals who have a strong family history of cancer. However, this strategy fails to identify a large proportion (over 40%) of ‘at risk’ people. Special attention needs to be given to some individuals known to more frequently carry BRCA alterations, such as populations of Ashkenazi Jewish, Swedish, Norwegian, and Icelandic origin.

Up to 1 in 40 Ashkenazi Jewish individuals carry such an alteration in the BRCA1&2 genes and hence are at increased risk. This is around 10-20 times higher than the general (non-Ashkenazi) population. In the Ashkenazi Jewish population only three alterations have been found to be very common and are called ‘founder mutations’.

What are the aims of the project?

• This study aims to identify the best method of screening the Ashkenazi Jewish population for individuals at increased risk of genetic cancer.
• This project compares the option of testing everyone with the current practise of testing only those with a high-risk family history.
• The project hopes to show that the approach of testing everyone would identify more carriers of gene alterations.
• It will also evaluate the acceptability and psychological impact of testing, the effect on quality of life, uptake of preventive options and the cost of such an approach.

The GCaPPS team aims to develop a strategy for prediction and prevention of genetic cancer. Over the long term it is hoped this will reduce cancers in the community.

What will the project provide?

GCaPPS will:

• Provide genetic counselling and education on the genetic risk of breast, ovarian and prostate cancer. This will help individuals decide if they wish to undergo testing.
• Provide lifestyle advice on reducing the risk of cancer.
• Offer a blood test to identify those individuals who have a BRCA gene alteration (founder mutation) and are therefore at higher risk of developing these cancers.
• Offer those found carrying a BRCA alteration options for early detection and cancer risk reduction or prevention.
• Refer ‘at risk’ individuals to genetic clinics to enable them to access preventive options.
• Provide post-test counselling support.
• Follow-up participants after testing to assess outcomes.

When does the project begin and how long will it last?

It is anticipated that the project will begin around the autumn of 2008. There will be an initial pilot phase which will screen 1000 individuals. This may take up to one year. This will be followed by the core phase of the project which hopes to screen 9,000 individuals and this may take up to 3 years. Individuals tested will be followed up for over 3 years to ascertain the impact of testing.

Who can participate?

Individuals over the age of 18 years who have four Ashkenazi grandparents can participate. The GCaPPS team at the Coordinating Centre at University College London (UCL) will assess and confirm your eligibility.

What will taking part involve?

You will need to attend a genetic counselling session provided by a genetic counsellor. This will be organised for you by the GCaPPS team. The counselling session and additional educational materials provided will help you decide if you wish to undergo genetic testing.
After receiving counselling if you decide to undergo testing you will be asked to provide a simple blood test.
All participants who have provided a blood sample will be divided into two groups. In the first group (Systematic Screening group) everyone will undergo testing. In the second group (Family History group) only those who have a high family history based risk of cancer will undergo testing. It may take 1-3 months to receive the test results.
A health questionnaire will be sent to you 7 days, 3 months, 1 year, 2 years and 3 years after you receive your test result. You need to fill this in and send it back by free-post.

Do I have to undergo testing?

No, you do not have to undergo genetic testing if you do not wish to. Testing is completely voluntary. Even if you decide to take part and change your mind later, you are free to withdraw from the project at any time and you do not have to give a reason. This will not affect any future care you receive.

Can I take part even if I do not want to get tested?

The GCaPPS team is interested in hearing from all eligible individuals even if they feel they do not want to take the test. If eligible you will be invited to attend the genetic counselling session. You can decide if you wish to get tested after counselling.

Is there any cost for having the test done?

No, there is no cost for joining the study or having the test done.

Where will I be tested?

Facilities for screening or testing will be available at a number of centres in the community. The different counselling centres are listed at the bottom of the page. You can choose to undergo counselling and testing at any centre convenient for you. Testing consists of a straight-forward blood test just like any other blood test.

There isn’t any cancer in my family – should I still undergo testing?

Although having a strong family history of cancer increases the likelihood of carrying a gene alteration, up to 4 in 10 individuals carrying the gene alteration may have no family history of cancer. Screening only those with family history may thus miss a number of individuals at risk. Therefore, it is still worth taking the test even if you do not have a family history of cancer.

How confidential is the genetic test?

The genetic test will be absolutely confidential. Any information provided will be stored on a secure username/password protected database. Your GP will be informed that you have agreed to take part (unless you request otherwise). Your participation in the study and all the information you supply will be treated as confidential and not released to anyone else outside the study.

What happens if I test positive?

A positive result indicates that you have inherited one of the three common BRCA gene alterations found in Ashkenazi Jews. This suggests that you are at a higher risk of developing breast, ovarian or prostate cancer.

If you test positive you will see a genetic counsellor, who will help guide and explain your options of managing your risk of developing cancer.
This includes:

• Lifestyle advice
• Medical prevention
• Screening: Yearly surveillance programmes starting at 30-35 years are available for early detection of breast cancer. You can decide to join ongoing research trials for early detection of ovarian and prostate cancer.
• Surgical prevention: Surgery to remove breast tissue or tubes and ovaries can prevent cancer.

The genetic counsellor will inform your GP and ensure that you are referred to a specialist genetic unit for further counselling and follow-up. You will be able to see relevant specialists and access these preventive options through the genetics clinic. The GCaPPS team will also keep in touch with you over the next 3 years.

What happens if I test negative?

If you test negative it is very likely that you have a low risk of developing BRCA related cancer i.e. you are not high risk. Your risk is similar to the rest of the general population. You will still be followed up by the GCaPPS team over the next 3 years.

What if I decide to withdraw from the study after joining it?

You are free to withdraw from the study at any time, through personal choice or without giving any reason for doing so.

Who are the doctors/scientists involved in the project?

The project will be run by health professionals under the leadership of Professor Ian Jacobs and coordinated by University College London. It is the result of collaborative work with a number of leading doctors and scientists both in the UK and overseas.
The investigators are:

• Prof Ian Jacobs (PI), Dr Usha Menon, Dr Ranjit Manchanda, Dr. Sue Gessler (Dept. Gynaecological Oncology, Insititute for Women's Health, UCL, UK)
• Prof. Jane Wardle (Health Behaviour Unit, Department of Epidemiology and Public Health, UCL, UK)
• Dr. Saskia Sanderson (NHGRI, National Institutes of Health, Bethesda, USA)
• Prof. Ian Tomlinson (Clinical Genetics, LRI, CRUK)
• Prof. Alistair McGuire (Health Economics, Department of Social Policy, London School of Economics, UK)
• Prof. Uziel Beller (Dept. of Gynecology, Shaare Zedek Medical Center, Faculty of Medicine, The Hebrew University of Jerusalem, Israel)

Who is funding the project?

The project is currently funded by the ‘The Eve Appeal’ charity which supports groundbreaking research into gynaecological cancers and by Boots as part of their ongoing support of The Eve Appeal.

What will happen to the results of the study?

The results of this study will be made available using scientific and medical publications that anyone can access. You will not be personally identified in any such publications.

Where can I get further information about the project?

If you are interested or wish to find out more about the project, you can send an email along with your name, address and telephone number to gcapps@ucl.ac.uk , or write to GCaPPS, c/o GCRC, Institute for Women’s Health, 1st Floor, Maple House, 149 Tottenham Court Road, London W1T 7DN. The web site is updated periodically and more information will be made available very soon.