Update on the work of the BAP1-interest group (BIG) consortium published

The BAP1-interest group (BIG) consortium (http://www.bap1.org/) was formed by Professor Nick Hayward and Dr Mohamed Abdel-Rahman as a way to put the minds of many international professionals together to work on research about the BAP1-Tumour Predisposition Syndrome (BAP1­-TPDS).  The Consortium recently published its first paper in the Journal of the National Cancer Institute reviewing BAP1­-TPDS families worldwide.

More information on the BAP1­-TPDS and the findings of the Consortium presented in this paper can now be found on the BAP1: a newly recognised melanoma gene and The BAP1-Interest Group (BIG) Consortium tabs respectively, under the Info for Patients menu.

Privacy Statement for Research on Melanoma carried out by the Section of Epidemiology and Biostatistics at the University of Leeds

The revised privacy statement detailing information for patients taking part in research studies carried out by the Section of Epidemiology and Biostatistics at the University of Leeds has been published. The statement can be found under the Info for Patients menu or by clicking the following link: Information for patients participating in our research studies.

Page last updated 16th February 2019

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.
  • For a few families with particular inherited mutations in the CDKN2A gene, and for families with newly identified melanoma susceptibility genes such as POT1 and TERT, the real risk of different cancers has not yet been established. These studies take many years to produce reliable estimates of risk and indeed if the mutations are very rare, then it might be difficult to estimate risk accurately. This is a problem as if we don’t yet know the risks of different cancer types it is very difficult to establish proper screening programmes. We will continue to try to further this research.
  • Clinical geneticists are trained to look at family history and to estimate risk and gene tests are improving all the time. If your family has a strong history of cancers (whether of melanoma or melanoma and other cancers) then you should consider asking for a referral to clinical genetics services to discuss risk and screening. Gene testing is an important part of what clinical geneticists do but is not an essential part of the consultation if patients decide against it.

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


Professor of Dermatology and lead research investigator.

Tel: +44 (0) 113 2064573


Mr Christy Walker


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.