Electronic Genealogy and Cancer Databases in Cancer Genetic Counselling

Abstract

The overall aim of this PhD thesis was to cohesively assess the availability and use of electronic genealogy databases and information from cancer registries to construct electronically generated pedigrees for risk assessment in genetic counselling. The thesis is built upon three published papers. Hereditary breast and ovarian cancer (HBOC), due to the Icelandic founder BRCA2 PV was used as an example. A second objective was to determine the optimal size of pedigrees for risk assessment in cancer genetic counselling. Three different approaches were used. Study I was a systematic literature review for articles describing the use of electronic genealogy and cancer databases in clinical service. Key findings: Published data on the use of such databases was limited, and the search identified only four articles fitting the search terms. Two of the papers were discussion papers. One of the four articles described an Icelandic study which applied information from the Genetical Committee of the University of Iceland. Study II was qualitative, on the experience of counsellees where electronically generated pedigrees (EGPs) were used in hereditary breast and ovarian cancer (HBOC) genetic counselling. Data was collected via an online focus group using an online discussion board. In genetic counselling, family health and genealogical history are collected to assess risk and clarify the inheritance mode of a suspected or known disorder. Key findings: Prior to genetic counselling, the majority of participants said that they had known about genetic counselling, and the most common reason for GC was a strong family history of cancer. Most participants were positive towards the use of electronic pedigrees and had trust in both the professionals and the information from the databases used to generate the pedigrees. Some, however, worried that insurance companies would obtain the information from the databases and possibly raise premiums or even deny insurance outright based on the information. Laws against genetic discrimination and the protection of personal data exist, both in health insurance and employment. The majority of participants had either unchanged or better family communication following genetic counselling. As relatives may have a diverse reaction to the offer of genetic testing, good family communication is essential. In Study III, the clinical use of electronically generated pedigrees was assessed, and the optimal pedigree size was calculated. Key findings: Using EGPs for risk assessment in cancer genetic counselling enabled accurate and comprehensive risk assessment in HBOC families. Further, such use is cost-effective and reduces work. We used Receiver Operation Curves (ROC) and C-statistics based on pair-wise comparison to evaluate the effect of pedigree size on the prediction of the presence of the Icelandic founder BRCA2 PV. Optimal results were attained using pedigrees with 3° relatives. Adding 4° relatives did not improve the outcome. Obtaining informed consent for the construction of pedigrees was straightforward, and no breaches of security (i.e. leakage of classified or restricted information) were observed. Conventional methods of collecting and constructing large enough pedigrees are time-consuming and difficult compared to our approach. This thesis reflects the experience of a clinical genetic service using electronically generated pedigrees in clinical practice. This approach is well established in Iceland and has been used for over 13 years in cancer genetic counselling. It is efficient and without complications such as breach of data and mistrust on behalf of the counsellees. A significant result from this work is that the optimal size of cancer pedigree, 3° pedigree which can take up to five generations. Such a pedigree is very difficult and impractical to generate using the conventional handmade technique. This should create a motive to use EGPs in other countries where some or all the resources are readily available.