SECTION FOUR: GENETIC AND MOLECULAR TESTING FOR CANCER
A small proportion of cancers is caused by inherited genes that predispose individuals carrying such genes to the development of malignant changes within their cells. Some inherited cancer predisposing genes result in rare forms of cancer such as retinoblastoma or multiple endocrine neoplasia. The proportion of more common cancers such as breast, colorectal or ovarian cancer caused by inherited genes is small, but the lifetime risks for those who have inherited the predisposing genes can be very high. Given that such inherited cancers often present in those who are younger than the age groups covered by national screening programmes, special arrangements are required for the identification, risk assessment and testing of such individuals.
"The field of genetic testing is about to explode in both its capacity and its ability to predict individuals at risk of cancer."
Better Cancer Care Consultation Respondent
Cancer Genetic Services
Scotland now has a coordinated cancer genetic service which is run from four regional genetic centres in Edinburgh, Glasgow, Dundee and Aberdeen. Specialist genetic counsellors work alongside clinical geneticists to raise awareness and facilitate the identification of those at risk. They provide individual risk assessment and advice for those who are, and who fear they are, at risk. Their role includes the 'triaging' of referrals, so that primary care can more effectively act as guardians for the specialist secondary service. Those patients deemed to be at lower or moderate risk are therefore supported by genetic counsellors in collaboration with the primary care team, whilst those who are at higher risk are seen within the specialist cancer genetic clinic.
Selecting the appropriate test for an individual requires highly specialised knowledge of diagnostic options and access to information about the latest developments in the field. Interpretation of the results requires expert understanding of the correlation between clinical and molecular findings. A significant investment has been made in Scotland's molecular genetic laboratories, to reduce the turnaround times for test results. The results for the full complex gene sequencing in, for example, the large genes associated with breast and large bowel cancer are now turned around within 40 days for the index case in a family (the first case to present in the family where the mutation is not known). This contrasts with response times of between one and three years in the past. The results of predictive tests on subsequent family members at risk, where the gene abnormality has already been identified, are usually available within ten days.
Scottish Molecular Genetics Consortium
The four molecular genetics laboratories in Scotland have, for some years, worked in a formal consortium arrangement as the Scottish Molecular Genetics Consortium, which is overseen by a steering group. The service is centrally commissioned and funded as a national service for Scotland. This arrangement has been highly successful and enables equity of access for all Scottish patients to a very comprehensive list of, often rare, molecular genetic tests. It also enables the retention of expertise for less common (or low volume) tests whilst avoiding the wasteful duplication that would occur if rare tests were done in all centres. Patients are seen and counselled by their local genetics service and the deoxyribosenucleic acid ( DNA) is sent to the nominated laboratory within the Consortium which has responsibility for providing the relevant test. The model has enabled both specialisation and rationalisation of provision for some more common tests.
The tests offered by the molecular genetics service use analysis of DNA to detect a range of genetic disorders. An important and relatively new area is the diagnosis and prediction of inherited forms of cancer and genetic testing for inherited bowel and breast cancer has been incorporated within the service available in Scotland. Molecular genetics laboratories play an important role in providing diagnostic testing for patients with inherited forms of cancer. They also offer pre-symptomatic testing for the specific genetic disorder in other family members at risk and, where appropriate, pre-natal diagnosis. Increasingly, molecular genetic tests are being used for patient management in other ways, such as targeting particular treatments for patients with specific genetic changes.
The four Scottish laboratories are also members of, and play a full part in, the recently established UK Genetic Testing Network. Through this mechanism tests can be arranged for Scottish families in other UK laboratories and Scottish laboratory expertise is made available for patients outside Scotland who have rare genetic disorders.
Following the publication of the Review of Genetics in Relation to Healthcare in Scotland in 2006 (the 'Calman Review') significant additional funding has been provided to upgrade clinical and laboratory facilities and recruit more staff to a range of medical, clinical, scientific, nursing, administrative and psychological functions within the genetic services in Scotland. Further investment of over £2 million per annum is now planned in Scotland's genetic services. This will increase the number of consultant geneticists and genetic counsellors who liaise between primary care teams and the genetic clinics and who provide a resource for carrying out necessary risk assessments. It will also enable NHS Boards to recruit clinical psychologists to offer psychological support, where appropriate, to people undergoing genetic tests. This reflects the anxieties that can be caused by the process of testing, waiting for results and considering the implications of genetic results.
The Scottish Government is also working in conjunction with the University of Edinburgh on a public engagement network which will involve the establishment of a formal, funded network, to not only link together all those from a variety of backgrounds who have an interest in enhancing public engagement with genetics, but will also provide a means of bringing together all those in social science and the humanities around Scotland who are working in this area of research. Through this network, it is hoped that public awareness of the important role that genetics can play in cancer and its treatment will be increased.
Following the 'Calman Review', the decision was taken to extend the work of the Molecular Genetics Consortium to include cytogenetic services (the study of chromosomes and cell division). The networked approach proposed offers the potential for cytogenetics to play an increasingly important role in the diagnosis and treatment of cancer, with treatments becoming tailored dependent on a person's genetic and physiological make-up and help to monitor the response to treatment in some patients.
Education of Healthcare Professionals to Enhance Identification and Understanding
As the proportion of cancer patients in which genetic aspects are known to be important increases, it will not be possible for genetic services to deal with the problem alone. It is vital that other professional groups are equipped with appropriate genetic knowledge so that they may become further involved. The Scottish Government will continue to fund NHS Education for Scotland ( NES) in their work with the Scottish Genetics Education Network and the Birmingham Genetics Education and Development Centre to enhance the genetic knowledge and skills of all healthcare professionals. This work will better equip those working in cancer services and primary care to be able to recognise the potential role of genetic factors in individual patients and offer appropriate advice and care.
To assist GPs and others to manage patients with a family history of cancer, guidance has been issued in Health Department Letter ( HDL) HDL (2001) 24 Cancer Genetics Services in Scotland: Guidance to Support the Implementation of Genetic Services for Breast, Ovarian and Colorectal Cancer Predisposition and HDL (2007) 08, Cancer Genetics Services in Scotland - Management of Women with a Family History of Breast Cancer. Understanding familial cancer risk may also inform a person's ability to plan for the future and ultimately impact on their lifestyle and healthcare decisions, family planning, or other decisions.
Example of Good Practice in Scotland
The West of Scotland Primary Care Group has developed a guidance for referral into Genetics services leaflet. The leaflet will be disseminated across all Community Health Partnerships and GP practices in the West of Scotland and clearly outlines:
- where all referrals should be sent to
- the type of information that should be included in a referral
- what the service can offer
- what the genetics risks are for breast, ovarian and colorectal cancers
- how to deal with patients who wish to have blood stored for possible future testing.
Molecular pathology is a scientific discipline that encompasses the development of molecular and genetic approaches to the diagnosis and classification of human tumours and will become the norm with major improvements in how diagnostic tissue is processed. There are two main areas where molecular pathology may have an impact on treatment and diagnostic services:
- Aiding diagnosis and classification of cancer
- Aiding assessment of treatment response and disease progression.
The role of molecular diagnostics must be integrated into routine practice and there is a need to examine how molecular pathology services are organised and provided across Scotland to ensure they are available to all cancer patients.
Access to tissue samples for research purposes is integral to understanding both tumour biology and the response to drug treatments. One of the ways to do this is to study the pathology of the tumour tissue and relate these findings to clinical and outcome data. Research capability should be embedded into the fabric of routine NHS cancer diagnosis and management in order to offer patients in Scotland the opportunity to contribute to research that will lead to future improvements in cancer prevention and care.
As part of the national audit for some cancers, mechanisms could be put in place that will enable patients to be asked whether they give their permission to donate some of their tissue for the purposes of research. There are, of course, many issues surrounding consent, storage and research and if these issues can be resolved, then the resultant population-based resource will facilitate research aimed at better understanding the differences between patient subgroups, disease causation and outcome correlates; ultimately leading to the potential for prevention and individualised treatments. A working group, to include patient representatives, will be convened to consider these issues further. It is important that Scottish tissue banks work to the same high standards as those required through licensing by the Human Tissue Authority.
- Invest in more genetic consultants, genetic counsellors, laboratory staff and appropriate psychological support to strengthen Cancer Genetic Services and meet recommendations made in the 'Calman Review' of Genetics
- Continue to support NHS Education for Scotland, Scottish Genetics Education Network and other stakeholders to enhance the genetic knowledge and skills of all healthcare professionals
- Update the protocols to identify the groups of high-risk individuals and stratify their risk and improve the organisation of the surveillance programme for those at high risk across Scotland
- Support the development of a public engagement network to raise awareness and understanding of the potential benefits of genetic services
- Explore the role of the molecular diagnostics models for achieving integration into routine practice
- Convene a short-life working group to advise the Scottish Government on the feasibility of national collection of tissue and consider, in conjunction with patients and other key stakeholders, the issues surrounding consent, storage, and access.