Information of participants in the Leeds University study of melanoma in families

MREC 99/3/45 – Studies of Familial Melanoma

In the years between 1989 and 2018, many individuals who have had melanoma or who have had melanoma in their families, took part in research led by Professor Julia Newton-Bishop. Research nurses Liz Pinney, Linda Whitaker and Susan Haynes worked with Julia for many years to collect information about family histories, to count moles on the skin and to take blood samples.

If you think you or a member of your family took part in this research we have some important information below, which we would like you to consider. But first however, a brief overview of the findings of this study.

In all, 2397 people took part in the study from all over England and Wales. The information provided has led to increased knowledge about many aspects of melanoma occurring in families. We have summarised many of the published academic papers and these lay summaries which can be accessed here.

The research showed:

  • That in many families with melanoma, family members have large numbers of moles (melanocytic naevi), but not all such families.
  • That even within “moley” families, melanoma can occur in family members with normal moles so that having larger numbers of moles than is usual is a poor guide to risk.
  • That the commonest inherited gene which increases melanoma risk is called CDKN2Aand the protein the gene produces is called p16. This gene is damaged (mutated) in the majority of families in England and Wales with 4 or more family members who have been affected with melanoma, but not all.
  • Families with mutations in the CDKN2Agene in the UK seem to be mainly at increased risk of melanoma of the skin. A few may also be at increased risk of pancreatic cancer or other cancers associated with smoking. For families with melanoma it is therefore important never to smoke, and to avoid sunburn as this is known to increase melanoma risk.
  • Rarer mutations in other genes have been found in recent years. These have been harder to find as they occur in only around 1%: 1 in 100 families. They occur in genes called POT1, TERT or BAP1. In these families, there is an increased risk of melanoma of the skin but some additional cancer types which differ according to the gene that is mutated.

Important information about the data we collected as part of this study

In order to carry out this research we collected data from families on family history which we have safe-guarded most carefully but which we now feel that we should make anonymous. We want to continue to work on the information but we feel that we should destroy the link between the information and family members’ details.  We want to do this to ensure that participants’ personal details remain safe in the long term, but it means that we would not be able to help if family members telephone us or e-mail to seek advice specifically about their families.

 

This information is provided here and will be left on the web site for 3 months before we destroy the link. If you have participated in the research and feel that there is a reason NOT to destroy the links for your family then please let us know by either of the e-mail addresses listed below or by these telephone numbers.

 

Date May 18th2018

We will continue to add new information to the web site in the future as new discoveries which may be of interest to families with melanoma.

 

Prof. Julia Newton-Bishop

j.a.newton-bishop@leeds.ac.uk

Professor of Dermatology and lead research investigator.

Tel: +44 (0) 113 2064573

 

Mr Christy Walker

C.L.R.Walker@leeds.ac.uk

Section Research Nurse

Tel: +44 (0) 113 2064575

Risks of cancers related to smoking in families with CDKN2A mutations

 

High risk of tobacco-related cancers in CDKN2A mutation-positive melanoma families.

Two research groups within GenoMEL have looked at the risk of cancers other than melanoma in families with inherited mutations in the p16 or CDKN2A gene: a group in Stockholm Sweden and another in Leiden, the Netherlands.

We have added a summary of the paper published by the Stockholm group in to the Plain Language Summaries section of the web site which is to be found in the Information for Patients. Both the Swedish and Dutch research groups showed that mutation carriers were at very significantly increased risk of smoking related cancers compared with people without the mutation.

Whilst these studies were conducted in two countries only it seems very important to advise families with mutations in this gene, that it is very important that they do not smoke tobacco,

 

 

Predictive Biomarker Research

A predictive biomarker is a test which provides information for medical teams and patients about how likely a particular treatment is to benefit that patient and or the risk of side effects. Using predictive biomarkers is an important part of the aim to deliver “personalised medicine”.  That is, that we need to move away from using the same treatment for everyone, towards choosing treatments more likely to work. There are in fact fewer predictive biomarkers actually being used in practice in 2017, than hoped. It has indeed proved difficult to develop such tests. These are some questions and answers about biomarker research.

Q. Why would treatments for advanced melanoma differ for different patients?

A. Melanoma is a cancer of pigment cells and all melanomas share some characteristics but they also differ: the genetic changes which define cancers occur in the cancer cells at random and cancers are all therefore a little different. Some changes are of no consequence but others mean that a particular drug may or may not to what it is intended to do. Similarly, only a proportion of patients develop most drug side effects and it may be that lifestyles, inherited difference between patients or other health issues play a role.  Personalised medicine aims to be able to predict side effects and whether or not a drug will work so that patients and their medical teams can choose the best option.

 

Q. Why has it been so difficult to find good predictive biomarkers?

A. There are many reasons. First it requires very large studies of many patients willing to give samples of their blood or their tumours: maybe thousands of patients being treated in many different clinics. Second, the patients need to be followed up for some time, and information about their response to the treatment carefully collected at each visit. Third, the tests performed must be chosen correctly based upon science, the samples must be collected and processed in exactly the same way in all the clinics, the chosen tests must perform very well in the laboratory and the analysis performed correctly. In fact the way to do the analyses optimally is still being developed using computer tests which are both statistical or a specialist statistical approach called “machine learning”. Finally, the scientific approaches to the analysis of samples is changing all the time: that is that options are increasing all the time and the treatment options are changing all the time so large scale studies set up to recruit sufficient patients and test them in a particular way must be “future proofed” so that the results stand the test of time.

Q. What will improve the identification of good biomarkers?

A. We think that the best way is to work together across the UK and internationally to perform large studies, using the best tests and getting the best analysis teams together. Indeed this is the view of the UK Medical Research Council which funds MRC Stratified Medicine Consortia. Some of the GenoMEL/MELGEN research groups have submitted an application in June 2017 to the MRC for a Melanoma Stratified Medicine consortium. It is very important to involve patients in discussions about research such as this and Professor Newton-Bishop presented the issues to the UK Melanoma Patient Conference in June 2017. We hope that some of the attendees at this meeting might advise the consortium if funded about how the research should be performed and how to develop a biomarker of meaningful value to patients. A link to this talk is provided here.

 

 

The second UK Melanoma Patient Conference

A summary by Professor Julia Newton-Bishop

The second Melanoma Patient Conference took place in Birmingham this year on June 16th and 17th. It was expertly organised (as was the first ever conference) by Imogen Cheese. It was very well attended by people who have experienced melanoma themselves or in their families, and representatives of the charities created to support melanoma patients. The speakers included medical staff treating melanoma patients, patients themselves and researchers. I think that this is a wonderful, and much needed event and I sincerely hope that it will continue and grow, supporting patients and enabling empowerment.

Filmed presentations are available on YouTube if you search for MPCUK2017. These include “Patient Voices” which, from the number of views recorded already, are very valuable.

 

The next UK Melanoma Patient Conference will take place on Friday and Saturday June 22nd and 23rd 2018. Registration will open in January 2018 and e-mail enquiries via enquiries@melanomapatientsconference.co.uk

 

 

 

How we in Leeds access on-going healthcare data about our research participants

 

The following information is provided for participants who consented to long-term follow up using information provided by Cancer Registries and the Office of National Statistics (ONS) as part of these studies:

 

The Melanoma Follow-Up and Case-Control Family Study. Ethics Committee number: MREC 01/3/057

A Genetic Epidemiological Study of Melanoma to Investigate The Protective Role Of Vitamin D For Relapse. Ethics Committee number: MREC 07/H1010/66

Vitamin D & Immunity in Melanoma: a study of the role of vitamin D3 and inflammation in immune reactions to cancer cells      REC reference:13/YH/0237

 

Why are we providing this information?

Participants in the two studies listed above were asked to consent to the use of information from the cancer registries and the Office of National Statistics about their health.

 

The way in which this information is supplied to researchers has changed and this information is intended to update participants so they know exactly what is entailed.

 

 

Why is this important to know?

The changes include ensuring greater transparency about how personal data (information such as cause of death or a new diagnosis of cancer) is handled. In other words, it is now crucial that participants in research studies know where researchers get data about them from, why they want it and what they do with those data. The organisation handling these data in the UK is now known as NHS Digital.

The information below is designed to make it clearer to melanoma patients taking part in the above studies (and/or their relatives) just how their data will be managed by NHS Digital and the University of Leeds in the future.

 

What data do we get from NHS Digital?

NHS Digital collect data about NHS patients and their illnesses. Research groups like ours can apply to NHS Digital to have some of those data for our research. The research studies, listed above, managed by the University of Leeds, were designed to look at a number of lifestyle factors in melanoma patients and how those factors might affect their health. We get most of this information directly from each patient but we also need to collect data from NHS Digital about two important aspects: Firstly; whether participants have had new cancers, and if so what type(s) and when were they diagnosed, and secondly; if they die, what was their cause of death and when did their death occur.

 

Why do we want this data?

Knowing these facts allows the research group to determine whether people who have had melanoma live for different period of time after diagnosis according to their lifestyle. Melanoma specialists can subsequently better advise melanoma patients on what lifestyle factors to adopt or avoid. Using NHS Digital is the best way of obtaining accurate data without accessing medical records held by GPs or hospitals and without repeatedly contacting the study participants.

 

What do we do with this data and how do we look after it?

Any data obtained can only be used for the purpose described in the participant information leaflet for that study. The data which are identifiable, including name and NHS number, will be seen only by a University of Leeds employee who will link the data provided by NHS Digital to the data collected directly from each participant by the research group. The staff analysing the research data cannot see that personal information. For both melanoma studies, we will seek information from NHS Digital until 2018 only. We will retain the research data but delete identifying information such as names, date of birth (we will use age at diagnosis in our analyses), addresses and NHS numbers.

 

What actually happens?

 

  • The research group in Leeds (led by Professor Newton-Bishop) will request information about cancers registered or death (as mentioned above).
    • The name, date of birth, sex, and where possible the NHS number of each participant is given securely to NHS Digital.
  • NHS Digital then supply any information they hold, such as registration of another cancer diagnosis, to the Senior Data Manager (currently May Chan).
  • That Senior Data Manager will add the new information to an existing master research record of the relevant patient. This research record is stored in a restricted database in a restricted area of the University of Leeds computer system. Only the Data Manager and a Research Nurse can access this database.
  • The data analysts and scientists working on the project will then ask for these data to enable their analysis. They make a formal request (via an application form) to a data access team comprised of; the Senior Data Manager and the Head of the Institute, who will review the application and if satisfied prepare and release only the necessary sections of the data. For example, the data will be labelled with a study number only.
  • In 2018, we will remove all names, dates of birth, addresses and other contact information from the master records so that the resource can be used in the future without risk to the confidentiality of participants.

 

 

What to do if you have concerns about asking NHS Digital for information

If you have any concerns then contact research nurse Christy Walker or Professor Newton-Bishop by email, or telephone 01132064575. Withdrawal from the study is possible at any stage. You may decide to withdraw only from further data collection via NHS Digital but stay in the study or you may in fact choose to withdraw all your data. If you chose to have your data destroyed, we will destroy all the data we hold, although we would not always be able to remove data already analysed.

 

 

Launch of Patient Decision Aid

Melanoma Focus (http://www.melanomafocus.com) has launched its Patient Decision Aid (PDA), whose aim is to inform people about melanoma and guide patients through the decisions they will need to take during their treatment.

By helping people to understand their options, this new online tool should improve the effectiveness of conversations between melanoma specialists and their patients.

The PDA may be accessed via http://melanomafocus.com/information-portal/pda/. Melanoma Focus hope clinicians and nurses will tell their patients about it.