GeneTalk Newsletter

Issue 5: August 2010

The need has been identified for better communication between scientists, healthcare practitioners and the public. GeneTalk aims to increase public awareness of the role genetics plays in health and disease. Dear Healthcare Professional In this issue of the Newsletter we would like to announce the date for the October 2010 GeneTalk events. Feedback is also given on the progress made over the past year in bringing molecular genetics into clinical practice. 5th Applied Genetics Workshop – 5 October 2010 (13h00-19h00) Public lecture for Breast Cancer Awareness – 5 October 2010 (9h30-12h00) Inter-University Wellness Project on the impact of hereditary factors on health outcomes Completion of the Genetic Knowledge Integration Project Medical Aid payment for the 70-gene MammaPrint gene profile as part of oncology benefits Ongoing research projects and education Forthcoming CPD event:  5th Applied Genetics Workshop Please join us for the next GeneTalk Workshop that promises to provide yet another important step towards the implementation of personalised medicine in daily clinical practice. Date & Time: 5 October 2010, from 14h00-20h00 (finger lunch from 13h00-14h00) Venue: Van der Horst Building, Room 201, Stellenbosch Business School, Bellville, Cape Town Registration fee:  R 250.00 per person. Free attendance offered to registered healthcare practitioners who complete a 3-page research questionnaire to be provided after registration. CPD accreditation: 1 Ethics and 4 Clinical points to be applied for Enquiries: Please contact Maritha at 021 9389324 or E-mail: lyndall@sun.ac.za Workshop Program: 14h00: Prof Johann Schneider - Introduction 14h30: Funding genetic testing in South Africa: what are the drivers? - Prof M de Klerk 15h15-16h00: The importance of multidisciplinary decision-making in breast cancer genetics - Dr E Myburgh TEA/COFFEE BREAK 16h15: The predictive value and cost-effectiveness of breast cancer gene profiling - Dr R Pienaar 17h00: Pathology supported genetic testing: Ethical considerations - Prof MJ Kotze 17h45-19h00: Discussion During the discussion session, Ronald van Klaveren will bring us up to speed with the latest research findings and applications in breast cancer transcriptional profiling done at Agendia in the Netherlands. BluePrint is one of the new additions to the MammaPrint service used to subtype breast cancer into Basal-type, Luminal-type and ERBB2-type intrinsic subgroups of tumours using advanced microarray analysis. Please register online at www.gknowmix.com or contact lyndall@sun.ac.za (tel. 021 9389324) for the registration form. Public lectures: Breast Cancer Awareness Please invite your patients with breast cancer or a family history of breast cancer to attend the public lecture (no cost) by Professor Justus Apffelstaedt of the Tygerberg Hospital Breast Cancer Clinic -  between 9h30-12h00 - at the above-mentioned venue. Some of our students and the clinicians involved in breast cancer genetic research and the Wellness Project (discussed below) will present their research aims and preliminary findings in short 15 minute slots. Topics include the impact of genetic variation on the metabolism of drugs used in cancer prevention like Tamoxifen, hormone replacement therapy (HRT) and food substances - such as caffeine, alcohol and folate - that may modify the (recurrence) risk of breast cancer (including BRCA gene mutation carriers) and other chronic diseases of lifestyle. A CANSA trained counsellor, Lujane Nutt, will co-ordinate future research activities to be discussed after the lectures. Prof Maritha Kotze was invited to present a talk on Breast Cancer Genetics and Well-being at the Vergelegen Medi-Clinic in Somerset-West on the 9th of October 2010. Wellness Research Project: Developing a practical approach to personalized medicine Completion of the sequencing of the human genome in 2003 led to the expectation that genomic information would lead to better medical diagnosis and treatment. It was the beginning of an era of personalised medicine, in which treatments would be tailored to an individual’s genetic make-up. The discovery that there are far fewer genes in the human genome than was originally estimated, however, challenged our understanding of the genetic basis of health and disease. It became apparent that a one-gene-one-disease association is the exception rather than the rule. We realised that knowledge of the structure of a gene would be incomplete without a deeper understanding of the mechanisms that drive the disease process. And so the journey began to develop a practical approach to personalised medicine by using pathology as the bridge between genetics and clinical practice. Genetic counselling to optimise clinical utility forms an integral component of this new approach in healthcare termed pathology supported genetic testing. In collaboration with researchers from the Department of Health and Wellness at the Cape University of Technology (CPUT), the Department of Pathology at the Tygerberg Academic Hospital initiated a project to develop a comprehensive gene-based wellness program. This project was prompted by the positive outcome of including an MRC-patented multi-gene test for cardiovascular disease (CVD) as part of a Wellness Program offered by a medical aid in Namibia about two years ago. A registered dietician, Charlotte Thiele, motivated the inclusion of genetic testing as part of their healthcare offering based on clinical experience. The same medical aid has approved further funding for screening of a group of their members who fulfils the clinical selection criteria for genetic testing.  Wellness Day: University of Stellenbosch, Tygerberg Campus The value of pathology supported genetic testing was made a little clearer on the 28th of July, 2010 during a Wellness Day arranged for the staff of the Faculty of Health Sciences at the Tygerberg Academic Hospital.  Dr Heloise Avenant of BluePrint Health, who is registered as a co-investigator in our ethically approved Wellness Project, presented guidance on the use of genetic testing for individuals with lifestyle-related conditions such as high blood pressure, diabetes, heart disease and stroke. Even more poignant was the value highlighted for members with a strong family history as a predictive factor of disease risk.  Professor Maritha Kotze was one of the participants with a family history of heart disease. The finding that her Discovery Age exactly matched her real age came as no surprise as knowledge of her genetic status empowers her on a daily basis to minimise potentially harmful gene-environment mismatches. Interested parties can sign up for participation in the research project if they fulfil the clinical selection criteria, by providing a saliva sample that will be used in genetic screening after signing an ethically approved informed consent form. Completion of the Genetic Knowledge Integration Project: 2007-2010 Insight gained from extensive research performed in the genetically distinct populations of South Africa over the past 20 years, paved the way for development of a computer-based medical device made freely available to clinicians who use genetic testing in their practice. With support from the Support Program for Industry Innovation (SPII) and the Innovation Centre of the Medical Research Council over the past three years, a method has been developed to incorporate clinical, biochemical/pathology, environmental and genetic information in a single test application. Genetic information derived from a panel of genes selected according to their phenotypic effects is correlated with the patient’s pathology/biochemical measurements to assess gene expression and/or response to treatment. By using this pathology supported genetic testing approach, the same principles applied in the past for use of high-penetrance mutations in genetic tests, can be extrapolated to low-penetrance genetics. Dissection of complex disorders into treatable subtypes and prevention of cumulative risk are important considerations. We have demonstrated the usefulness of this combinational approach in patients at risk of cardiovascular disease (CVD) and the latest research findings will be presented by Dr Dawie van Velden at a Congress in Italy later this year. Heart disease provides a model to address the lifestyle link in most chronic diseases with a genetic component. It has been estimated that at least 30% of cancers can be prevented by risk-reduction recommendations for healthy body weight, physical activity and diet. Research is underway to determine the clinical utility of combining lifestyle information with breast cancer genetic testing applications performed in a clinical setting. 70-gene MammaPrint gene profile: Medical Aid payment as part of oncology benefits Oncology is leading the way in personalised medicine, as it is fast becoming the norm for breast cancer patients to have their genetic material tested to select the best treatment option. One test option used to select patients who are most likely to benefit from chemotherapy is the MammaPrint, a comprehensive 70-gene profile and the only FDA-cleared breast cancer recurrence test. Despite the relatively high cost, MammaPrint is reimbursed by an increasing number of medical schemes in South Africa as it can reduce the use of chemotherapy with about one-third. This is due to the efforts of a group of surgeons, oncologists and Prof Manie de Klerk of Qualsa, who developed an algorithm for use of this test in oestrogen-positive breast cancer patients. These guidelines were incorporated into the Gknowmix software program to identify breast cancer patients where MammaPrint is clinically indicated. The highly accurate MammaPrint test identifies patients with early metastasis risk, who are likely to develop metastases within five years following surgery. Several authoritative studies have shown that chemotherapy particularly reduces early metastasis risk and in planning treatment, the MammaPrint test results provide doctors with a clear rationale to assess the benefit of chemotherapy in addition to other clinical information and pathology tests. The TargetPrint test is added at no additional cost, to provide objective, quantitative information about the expression of the specific tumor-related proteins, ER, PR and Her-2neu, while a new addition called BluePrint classifies tumours into treatment-directed subtypes. DiscoverPrint furthermore measures the expression of the whole genome for all patients enrolled in a research study, to eventually allow the identification of investigational drugs that offer the most benefit for women with certain tumor characteristics. Ongoing research and development commitments continue to augment the ability to accurately predict breast cancer recurrence and sub-typing, and help physicians tailor individual treatment plans to their patients. The goal of the testing laboratory, Agendia, is to provide women with answers to crucial treatment questions, such as how their breast cancer will respond to targeted therapies or various chemotherapy regimens. Pre-selection of medication that can block the effect of a faulty gene or avoidance of drugs that are unlikely to work due to the genetic make-up of the patient, paves the way for cost-effective, patient-centered care. Savings can however only be realised if action is taken to reduce recurrence risk or prevent the complications of the disease that is predicted based partly on the genetic test results. To simplify this process, the Gknowmix database tool can now assist clinicians with the test selection and service delivery process, and its use has also been linked to ethically approved health outcomes research projects. Ongoing Research Projects and Education Participation in the GeneTalk events is a great way to stay up to speed with genomic research. It is also an opportunity to learn and to be educated about how the outcome of research projects can influence healthcare and patient care. It is not an easy task to translate the complexity of the field of genomics into practical clinical applications. Therefore several translational research projects that involve both a service and research component have been initiated as a collaborative effort between the private and public sector. In a “Call to Action” recently published in the June 2010 issue of the Journal of Clinical Pathology, it was pointed out that the medical profession is lagging behind the technology and business communities in preparing for the application of personalised medicine. As a critical step in leading the change to a new medical model, these authors developed a personalised medicine curriculum that could catalyze the adoption of similar training modules throughout North America. South African universities have not stayed behind in preparing clinicians for the new era of personalised medicine. Prof Maritha Kotze will present lectures to pathology registrars on the topics of Pharmacogenetics and Nutrigenetics on the 11th and 13th of October, respectively, and is actively involved in the training of postgraduate students in these new fields through participation in translational research projects. A web-based distance-learning course that includes certain components of these educational materials and highlights the importance of genetic counselling (by clinicians/genetic counsellors) is also offered to private practicing clinicians with a special interest in Integrative Medicine. Contact us For more information please contact Prof Maritha Kotze at 021 9389324 / 0828799108 or email maritha@gknowmix.com or maritha@sun.ac.za.

GeneTalk Newsletter

Issue 4: August 2009

The need has been identified for better communication between scientists, healthcare practitioners and the public. GeneTalk aims to increase public awareness of the role genetics plays in health and disease.

CPD-accredited workshop: September 2009

A series of workshops will be held on heart health and cancer risk reduction during Heart Month on 18-19 September and 23 September in Cape Town and Durban, respectively. Research on the complex interplay between genes and the environment revealed that the best ways to avoid cancer are similar to those needed to prevent obesity and heart disease as well. Furthermore, in patients with existing disease, response to therapy may be genetically determined. In relation to cancer, the focus will be on breast cancer in preparation of Breast Cancer Awareness Month in October. There is no evidence for one-size-fits-all in the era of evidence-based medicine, therefore genetic testing is becoming increasingly important to individualise therapy.

International speakers: Ronald van Klaveren of Agendia in the Netherlands will discuss the benefits of the FDA approved MammaPrint test which aims to help physicians decide which treatment strategy is most appropriate for each individual breast cancer patient. Chemotherapy is the most dreaded part of breast cancer therapy and is only effective in 10-20% of patients. Based on a study published in February 2009, the 70-gene MammaPrint test not only identifies patients with a poor prognosis more accurately, but also confirms that the chemotherapy will improve the poor prognosis.

Elaine Warburton and Jonathan O’Halloran of the UK based company QuantuMDx will provide participants with a glimpse into the future of nanotechnology for application in molecular diagnostics. Jonathan has recently joined the Pathology Research Facility at Stellenbosch University to develop a hand-held point-of-care-device that holds great potential to reduce the cost of genetic tests. These three speakers will be presenting at both the Cape Town and Durban workshops.

Local presentations include: Prof Johann Schneider, the head of Pathology at the University of Stellenbosch, will open the GeneTalk event at the Tygerberg Campus (21/9/09). He will provide a historical overview of pathology as a bridge between molecular genetics and clinical medicine in relation to a new approach in healthcare, termed Pathology Supported Genetic Testing^TM.

Prof Tony Bunn, the head of the Innovation Centre at the Medical Research Council, will open the workshop in Durban (23/9/09), following attendance of the Bio2Biz Congress in Durban where Dr Maritha Kotze will present an invited lecture entitled “Gknowmix: The gateway to genomic healthcare”. Her talk at the GeneTalk workshop in Durban will also focus on the integrated Gknowmix service delivery system developed over the past two years with support from the Industrial Development Corporation of South Africa. Already in 2006, the idea of a web-based genetic service platform has been presented to the Ethics Review Committee of the South African Medical Research Council and their recommendations taken into account. Prof Bunn will discuss the rollout of this genetics business model in clinical practice and would welcome input from other healthcare professionals to guide the process. This initiative involves the use of information technology to further research and to improve patient care. It has been said that “in medicine the computer is to memory what the X-ray machine is to vision”.

Highlights: Prof Keymanthri Moodley of the Bioethics Unit, University of Stellenbosch, will discuss the ethical aspects of genetic testing. Her talk will include a case study where genetic testing for the “caffeine gene” linked to increased risk of hypertension and heart disease when consuming too much coffee was requested. This test is offered internationally by the Google-sponsored direct-to-consumer company 23andMe. Dr Heloise Avenant recently attended the “Direct-to-Consumer” Genetics Conference in Boston, USA, and will share her experience from a GPs point of view. Prof Bongani Mayosi of Groote Schuur Hospital will discuss the impact of molecular genetics on clinical cardiology with a special focus on research and service delivery. Dr Lucille Heslop of Durban Oncology, Prof Justus Apffelstaedt of the Dept of Surgery, Tygerberg Hospital, and Drs Ettienne Myburgh and Rika Pienaar of Panorama Hospital, will discuss genomic applications in breast cancer. Importantly, Prof Manie de Klerk will discuss the process followed by Qualsa, one of the largest Managed Care Companies in South Africa, to assess payment of a 70-gene profile (MammaPrint) for selection of chemotherapy treatment in breast cancer patients.

Accreditation: The workshop was accredited with 2 ethics and 5 clinical CPD points by the HPCSA. Please register at www.gknowmix.com to view the full program including 18 speakers or to register for the workshop, or contact Dr Maritha Kotze (Tel. 021 9389324 / 0828799108; email: maritha@gknowmix.com) for the program and registration form. A reduced fee of R300 per day per person applies for early registration before 1 September 2009. The registration fee includes educational material and continued support for genetic testing requirements through our Genetic Care Centre at http://www.genecare.biz/.

Workshop Feedback: Iron Disorders GeneTalk

The workshop on Iron Disorders and Well-being held in May 2009 as part of the GeneTalk series was attended by approximately 40 healthcare professionals. We were privileged to have Prof Tracey Rouault, who heads up the Molecular Medicine Program on Human Iron Metabolism of the NIH in Bethesda, USA, as a speaker at this workshop.

The research on the genetic aspects of haemochromatosis in the SA population was initiated at the University of Stellenbosch more than 10 years ago. Identification of the spectrum of risk factors underlying this preventable genetic disorder provides a major healthcare opportunity to reduce the burden of heart disease, cancer, diabetes, arthritis, infertility and many other complications of organ damage in the population. New insights gained from the workshop formed the basis of an invited book review on iron metabolism. This article provides the scientific back-up for application of Pathology Supported Genetic Testing^TM to confirm or exclude hereditary haemochromatosis (HH) in patients with raised ferritin levels. This new test concept requires (1) that genetic testing is performed within a specific pathology/biochemical and clinical profile that also defines the test selection criteria, (2) that the patient report contains both the pathology and genetic test results where appropriate with an interpretation for clinical application, and (3) that gene expression and monitoring of response to treatment are assessed through the accompanying pathology/biochemical parameters included with genetic testing.

Genetic counselling

Genetic counselling forms an integral part of the activities of the Genetic Care Centre linked to the Gknowmix genetic testing service delivery system. Please contact Dr Maritha Kotze (021 9389324 / 0828799108) or registered genetic counsellors Frieda Loubser and Julie Malan via our website or email counselling@gknowmix.com.

15 May 2009 - GeneTalk Issue 3

The need has been identified for better communication between scientists, healthcare practitioners and the public. GeneTalk aims to increase public awareness of the role genetics plays in health and disease.

Forthcoming CPD-accredited Workshop

A full-day workshop will be held at the Faculty of Health Sciences, University of Stellenbosch, on the 27th of May 2009, during Haemochromatosis Awareness Week. The aim is to keep healthcare practitioners informed about new developments in the ever changing world of iron-related diseases, due to major advances in genetics and molecular biology.

• International speaker: Prof Tracey Rouault, head of the Molecular Medicine Program on Human Iron Metabolism of the NIH in Bethesda, USA, will discuss the role of iron homeostasis in anaemia and neurodegeneration.

• Local contributions: The workshop will be opened with an overview on Iron Disorders in Haematology, by Prof Akin Abayomi, the new head of the Division of Haematology at the University of Stellenbosch and NHLS. Other relevant topics will be covered by Drs Susan van Rensburg, Johan van Wyk, Erna Mansvelt, Dawie van Velden, Maritha Kotze, Corne Kruger, Jeanine Marnewick and registered genetic counsellor Frieda Loubser.

Highlights: The research findings of Dr Corne Kruger of Durbanville Medi-Clinic, who completed his PhD degree on non-alcoholic fatty liver disease (NAFLD) in December 2008 will be discussed in the context of our new approach of pathology supported genetic testing. NAFLD is a common liver disease and independent predictor of cardiovascular events. Haemochromatosis mutations appear to play a role in the severity of NAFLD. As part of her talk, Dr Erna Mansvelt will address specific questions received by the Genetic Care Centre from clinicians (including Dr S van Blerk of Swellendam who will be attending) on the diagnosis and treatment of patients with abnormal iron stores. Dr Jeanine Marnewick of the Faculty of Health and Wellness Sciences at the Cape Peninsula University of Technology will provide scientific evidence of the anti-oxidant effects of Rooibos tea, which contains iron. Kirsten Alberts of the Haemochromatosis Society of South Africa will present the closing remarks.

Accreditation: The workshop was accredited with 2 ethics and 5 clinical CPD points by the HPCSA. To view the full program including 10 speakers and to register for the workshop, please register by 22/5/09 at www.gknowmix.com or email maritha@gknowmix.com for the registration form. The cost is R 900 per person and includes educational material and continued support for genetic testing needs through our Genetic Care Centre @ www.genecare.biz.

Workshop Feedback: Breast Cancer GeneTalk

Two Breast Cancer Workshops held during October 2008 in Pretoria and Cape Town, were attended by more than 100 healthcare professionals. Based on the knowledge that breast cancer is caused by genetic abnormalities (mutations) that are either inherited or acquired, a comprehensive Breast Cancer GeneScreen was introduced at this event. This service includes genetic counselling, testing for familial breast cancer (BRCA1/2 Gene Test) and cancer prognostication (MammaPrint 70-gene Microarray Test). As a new addition to the microarray analysis, HER2/neu, oestrogen receptor (ER) and progesterone receptor (PR) status is also determined (at no additional cost) by using the TargetPrint service to direct cancer treatment at the cause of the disease.

An important outcome of the Breast Cancer workshops was a request from one of the largest managed healthcare organisations in South Africa to submit a Health Technology Assessment for medical aid cover of the MammaPrint breast cancer prognosis test. Interaction thereafter was cordial and constructive. Many medical aids now pay for the MammaPrint test which could save chemotherapy in about one-third of breast cancer patients.

Dr Maritha Kotze was invited by Dr Carol-Ann Benn to present new developments in breast cancer genetics at the Surgical Oncology Congress earlier this year. Further input from several local oncologists and surgeons contributed to the development of more specific test criteria for use of MammaPrint in South Africa, to accurately subclassify patients with early-stage breast cancer into High- and Low-risk groups of disease recurrence. This enables cost-effective implementation of Mammaprint in clinical practice as a prognostic marker for breast cancer. For more information please contact Dr Ettienne Myburgh (surgery@mweb.co.za), who contributed to the development of an algorithm for use on the Gknowmix website for this purpose. He will present this new approach at the next Breast Cancer Workshop planned for 18/19 September 2009 in Cape Town.

Haemochromatosis: Opportunity for disease prevention

Reducing the risk of cancer, heart disease, diabetes, arthritis, infertility and many other complications of organ damage due to overabsorption of iron from the diet has become a health priority. Haemochromatosis has been classified as the most common genetic disorder worldwide. In Caucasian populations, approximately one in ten people carry a faulty gene which, when inherited from both parents, could lead to iron overload if preventative measures are not implemented at an early stage.

Everybody should take notice of the potential danger of inherited iron overload as it starts with the same symptoms as iron deficiency, namely chronic fatigue. When feeling tired, many people assume iron deficiency and take iron supplements. The degree of iron overload, if any, depends on interaction between genetic (low penetrance) and environmental factors. Individuals with a genetic predisposition for haemochromatosis respond differently to iron intake due to gene-diet interaction, a concept termed nutrigenetics.

Pathology Supported Genetic Testing^TM

Haemochromatosis provides an excellent example of a complex disease that is best addressed by a pathology supported genetic testing approach. What this means, is that genetic testing for haemochromatosis is 1) performed within a specific pathology/biochemical and clinical profile that defines the test selection criteria, 2) both the biochemical and genetic test results are provided in the patient report together with the interpretation for clinical application, and 3) gene expression and/or response to treatment is monitored through these accompanying genetic test parameters.

Until recently, the HFE gene was considered the only major cause of inherited iron overload. Failure to identify mutations in a relatively large number of patients referred by clinicians for genetic testing contributed to the identification of several other genes involved in iron overload. It also highlighted the importance of a step-wise approach in the diagnosis and treatment of iron overload disorders (Brissot et al. 2008 Blood Reviews Vol. 22: 195-210).

Pathology supported genetic testing in patients at risk of haemochromatosis involves the following steps to be discussed at the workshop for future implementation:

1. Consider iron overload based on presenting clinical features and iron status, taking into account the main confounding factors such as alcoholism, inflammatory conditions, acute or chronic hepatitis and polymetabolic syndrome.

2. Evaluate hepatic vs splenic iron load in order to direct the diagnosis to the most likely cause of iron excess.

3. Rule out acquired iron overload due to external factors such as prolonged iron supplementation (e.g. in the setting of competitive sports) or repeated transfusions in patients with haematological diseases, represented by chronic anaemias such as thalassaemia major and sickle cell disease.

4. Identify the genetic origin of iron overload by considering both family and personal information (e.g. plasma ceruloplasmin level when transferrin saturation is normal or low).

5. Treat patients with iron overload according to genetic subtype: venesection is the treatment of choice in patients with haemochromatosis related to hepcidin deficiency, but is poorly tolerated or contraindicated in patients with iron overload due to ferroportin failure.

6. Monitor treatment response by assessment of relevant biochemical parameters and health outcomes.

A project is underway to develop a comprehensive Iron Disorders Gene Screen that will not only focus on the identification or exclusion of genetic risk factors, but also the documentation of clinical conditions (e.g. NAFLD), abnormal biochemistry and environmental factors that may contribute to haemochromatosis-related medical conditions.

Key Reference: Brissot P et al. Current approach to hemochromatosis. Blood Reviews 2008; 22: 195-210.

Genetic counselling

Genetic counselling forms an integral part of the activities of the Genetic Care Centre linked to the Gknowmix genetic testing service delivery system. Please contact Dr Maritha Kotze (021 9389324 / 0828799108) or registered genetic counsellors Frieda Loubser and Julie Malan via our website or email counselling@gknowmix.com.

When the first announcement of the GeneTalk Workshop in Iron Disorders and Well-being was distributed earlier this year, we received several requests for similar events in other regions of South Africa. Based on their clinical experience, Dr Hein Badenhorst and Prof Nola Dippenaar arranged a satellite meeting earlier this month in Pretoria that formed part of our CPD program to inform healthcare practitioners about the role of genetics in health and disease management.

22 August 2008
GeneTalk Issue 2 - Breast Cancer Focus

Upcoming Events: Breast Cancer Workshops 9 & 11 October 2008

Breast cancer kills about 400 000 women worldwide each year, and 800 000 more cases are diagnosed annually. In South Africa, more than 4000 women are diagnosed with breast cancer every year and about 40% of them die from the disease. The high-penetrance BRCA1 and BRCA2 genes explain less than 5% of the total breast cancer incidence and approximately 25% of the familial risk. Recent studies provided scientific evidence that a large proportion of the familial risk of breast cancer is due to multiple genes that interact with each other and the environment. Several genetic tests became available during recent years for breast cancer prognosis and prediction of treatment response. To keep healthcare practitioners up to date with these developments, we arranged two CPD accredited workshops during Breast Cancer Month.
The following topics will be covered during two full-day workshops from 8h30-16h30 arranged at the Universities of Stellenbosch (11/10/08) and Pretoria (9/10/08):

• Modern breast health management - Prof Justus Apffelstaedt & Dr Karen Baatjes
• Clinical application of the 70-gene MammaPrint test in South Africa - Dr Rika Pienaar
• FDA approval of MammaPrint for clinical use - R van Klaveren (Agendia, Netherlands)
• Hormonal prevention of breast cancer - Prof Greta Dreyer
• Breast cancer pathology and prognostic indicators - Dr Karen Brundyn
• Genetic counselling for familial breast cancer (BRCA1/2) - Frieda Loubser & Julie Malan
• Obesity and breast cancer risk - Prof Nola Dippenaar
• How the interplay between genes and environment increase cancer risk - Dr Dawie van Velden & Dr H Badenhorst
• Update on breast cancer tests available in South Africa - Dr Maritha Kotze

Click here to view more details and to register online or email lyndall@sun.ac.za for the form or more information. The cost is R600 per person.

Pathology-supported gene-based intervention

The Genome Research Innovation Initiative launched in association with the University of Stellenbosch in April 2008, provided the gateway for a new approach of pathology supported gene-based intervention. Applied Genetics Workshops arranged in Cape Town and Johannesburg at the time, educated healthcare professionals in clinical application of the Cardiovascular and Wellness Genescreens featured at Gknowmix.com. It involves the following steps using a multi-disciplinary approach:

1. Document family history and evaluate the patient's current health status
2. Choose appropriate genetic test(s) based on medical history and pathology
3. Combine information obtained in 1 and 2 into an informative test report, providing risk implications and health guidelines in relation to gene expression, if any
4. Apply test information for risk reduction intervention/treatment based on genetic prognostication, gene-drug (pharmacogenetics) and gene-diet (nutrigenetics) interactions, as appropriate
5. Monitor response to treatment as part of compliance management

How to request a test online

Although the development phase took longer than expected, requests for the Cardiovascular and Wellness Genescreens and genetic counselling services can now be processed online at www.gknowmix.com. This requires registration of the consulting healthcare practitioner either at referral, or following an email request by the client (generated from the website) to become the consulting clinician. The relevant test request form needs to be completed online to provide the information required for report generation upon completion of the genetic test. Once payment has been made, the sample will be collected for processing at the laboratory. The Breast Cancer Genescreen, including different test options based on the family history and health status of the patient, will be launched at the workshops in October 2008 using a similar approach. All information entered into the Gknowmix database is encrypted for security purposes, using the HTTPS protocol.

Cardiovascular GeneTalk at the Nutrition and Clinical Sports Medicine Conferences

The clinical usefulness of genetic testing was assessed as part of a nutrition intervention study in South African patients with the metabolic syndrome. Use of the multi-gene CVD assay in these patients could partly explain differential responses to nutrition intervention (nutrigenetics). Dr Dawie van Velden will discuss these results at the forthcoming Nutrition Congress in Pretoria (29/9/08). Dr Maritha Kotze will talk about the "Application of cardiovascular genetics in chronic disease risk management" at the Clinical Sports Medicine Conference (10/10/08), on invitation by Prof Martin Schwellus of the South African Sport Science Institute.

Haemochromatosis GeneTalk at the SAGES Congress, 9 August 2008

Drs Corne Kruger and Maritha Kotze discussed the impact of haemochromatosis mutations on severity of non-alcoholic fatty liver disease in South African patients, of which the majority was also diagnosed with metabolic syndrome. This research forms part of the PhD study of Dr Kruger, a private practicing gastroenterologist/physician at the Durbanville Medi-Clinic.
Haemochromatosis was selected for initiation of the GeneTalk Public awareness campaign in May 2008, since it represents a major opportunity to reduce the burden of cancer, heart disease, diabetes, arthritis, infertility and many other complications of organ damage due to over-absorption of iron from the diet. The Haemochromatosis Society can be contacted at http://www.haemochromatosisza.org/.

Genetic counselling

Genetic counselling forms an integral part of activities at Genetic Care Centres, linked to the Gknowmix genetic testing service delivery system. Please contact Dr Maritha Kotze (021 9389324 / 0828799108) or registered genetic counsellors Frieda Loubser and Julie Malan for more information via our website.

29 May 2008
GeneTalk Issue1 - Iron Overload Focus

GeneTalk aims to increase public awareness of the role genetics plays in health and disease. This initiative has been launched in collaboration with the South African Haemochromatosis Society, a non-profit organization established in 1987 to make healthcare practitioners and the public more aware of the early clinical features of hereditary haemochromatosis, a common iron overload disorder. Haemochromatosis provides the best example of a serious late-onset genetic disorder that can be prevented by early diagnosis and treatment.

The impact of iron metabolism on chronic disorders such as arthritis and multiple sclerosis has been discussed by Prof A Kalla and Dr MJ Kotze on the 29th of May 2008, at the Western Province Blood Transfusion Services in Pinelands, Cape Town. This event and a radio interview on SAFM formed part of the program for International Haemochromatosis Awareness Week, from 24-31 May.

Iron overload can be deadly

Haemochromatosis has been classified as the most common genetic disorder worldwide. In Caucasian populations, approximately one in ten people carry a faulty gene causing hereditary haemochromatosis. In most cases the disease will only develop when a defective gene is inherited from both parents. The degree of iron overload, if any, depends on interaction between genetic and environmental factors. Everybody should take notice of the potential danger of inherited iron overload as it starts with the same symptoms as iron deficiency: Chronic fatigue. When feeling tired many people assume iron deficiency and take iron supplements. Individuals with a genetic predisposition for haemochromatosis respond differently to iron intake due to gene-diet interaction, a concept termed nutrigenetics. Vegetarians or regular blood donors may be protected from iron overload and never develop the disease despite having a genetic predisposition for haemochromatosis. This presents a classic example of how the expression of a faulty gene can be modified through changing the environment. In affected patients with high body iron stores regular phlebotomy is required to treat haemochromatosis.

It is important to know that iron build-up can be prevented by some of the body's normal physiological processes, for example menstruation in women. Around middle age the stores of iron may accumulate to such an extent in haemochromatosis sufferers that excess iron is deposited in various organs. This accumulation, if left untreated, can lead to organ damage and serious illnesses, including liver cirrhosis, cancer, heart failure, diabetes and arthritis. For this reason, the analysis of the most common genetic risk factor for haemochromatosis, mutation C282Y, is included as part of our comprehensive Wellness GeneScreen for chronic disease risk management. A single-gene diagnostic test for haemochromatosis performed in conjunction with serum iron studies is also available.

Genetic counselling

The haemochromatosis public awareness campaign is underpinned by genetic counselling services offered at Genetic Care Centres linked to the Gknowmix genetic testing service delivery system. Please contact Dr Maritha Kotze (021 9389324 / 0828799108) or registered genetic counsellors Frieda Loubser (Cape Town) and Julie Malan (Gauteng) for more information via this website. The Haemochromatosis Society can be contacted at www.haemochromatosisza.org.

Feedback: Applied Genetics Workshops 12 & 18 April 2008

The Genome Research Innovation Initiative was launched in association with the University of Stellenbosch during April 2008. Two training workshops attended by nearly 100 health professionals in Johannesburg and Cape Town opened the way to a new approach in healthcare: Pathology supported gene-based intervention. Prof Jimmy Volmink, the Deputy Dean of Research at the Faculty of Health Sciences, University of Stellenbosch, opened the workshop in Cape Town with an enlightening introduction to the "brave new world" of genetics. He expressed the hope that many more workshops of this nature facilitated by Dr Maritha Kotze will be organised in future to promote genome research innovation.

The workshops were accredited with 4 clinical and 2 ethics CPD points, and the handout entitled "Genetics in Family Practice" was also accredited by StellMed.

The first speaker at The Cape Town Workshop, Prof Rajiv Erasmus, head of Chemical Pathology at Tygerberg Hospital, gave an excellent talk on wellness. He defined wellness as a state of mind that encourages healthy behaviour. People have many excuses for not changing their lifestyle to improve their health. These include lack of knowledge, too much effort, that changing habits will only add more stress to their already stressfull lives. However, increasing awareness of the fact that nutrition determines 40-60% of the average person's health, and that genetic functions can be changed by what we eat, has led to a paradigm shift as more and more people take control of their health. Dr Hein Badenhorst, a GP of Gauteng and Dr Dawie van Velden also gave their views on the wellness paradigm. The question was raised how healthcare practitioners - in light of what is available today - could practice medicine, wellness, dietetics, etc. without incorporating genetics in clinical practice.

Dr Maritha Kotze explained why genetic testing should be applied in chronic disease risk management and wellness programs. A one-size-fits-all approach does not work as the response to medication and nutrition intervention may differ between individuals due to their genetic background. According to a MRC report cardiovascular diseases related to hypertension, high cholesterol and diabetes killed 565 South Africans daily in 2000. This number is expected to rise to approximately 700 by the year 2010 if a more effective method to reduce disease risk is not implemented. Prof Nola Dippenaar and Dr Susan van Rensburg provided scientific evidence of the importance of assessing a person's genetic risk in the context of metabolic indicators and lifestyle factors. Celeste Naude of the Division of Nutrition, University of Stellenbosch, furthermore provided an excellent overview of the nutritional genomics in the context of chronic disease risk management. Sarita Banitz, one of the first registered dieticians in South Africa to embrace the science of nutrigenetics, discussed her successes of incorporating genetic testing in private practice.

Genetic counselling, ethics and insurance issues were discussed by the genetic counsellors Julie Malan (Gauteng) and Frieda Loubser (Cape Town). Ethical issues may arise when a genetic predisposition is identified in a healthy individual without any disease symptoms. Therefore the individual's current health status, family history and ethnic risk are important considerations when a genetic test is requested. Once a gene defect has been identified in an individual with clinical features of the disease in question, the genetic test result would not in itself have a major impact on insurance. A serious illness or strong family history of the disease is usually sufficient to classify someone as high risk. In these instances the benefits of laboratory testing may outweigh the risk of genetic discrimination since the presence of the disease-causing mutation may be excluded, or if detected, preventative treatment may be possible.

Ripple of Hope

An inspiring talk recently presented at the University of Cape Town by Dr Michael Hayden highlighted the importance of open discussion about the devastating effect an incurable genetic disorder such as Huntington's disease could have in families. New scientific discoveries provide hope to those affected and has to be communicated in a responsible manner.

All of us carry a number of faulty genes that may vary widely in their expression patterns due to other genetic and environmental influences. While DNA analysis enables pre-clinical diagnosis of individuals with a faulty gene for Huntington's disease before the disease manifests itself - "the curtain is lifted" - most genetic tests available today provide information that can be used to change someone's genetic and health destiny. The saying "Identify an affected individual and save a family" applies not only to hereditary haemochromatosis, but also to many other medical conditions with a genetic component.