Establishing cancer genomics registry to support implementation of personalised medicine – Prof Kotze
Prof Maritha J Kotze
- Department of Pathology, Faculty of Health Sciences, University of Stellenbosch
- Biography of Prof Kotze
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Title of the project
Establishing a cancer genomics registry to support the implementation of personalised medicine
The overarching objective of the proposed project is to establish a local breast cancer genomics patient registry envisioned as a practical alternative to prospective clinical trials for validation of the clinical utility of new genomic applications.
A database resource for translational oncogenomic research was established during the introduction of a microarray-based gene expression profiling test for early-stage breast carcinoma in South Africa. The on-going development of this registry has facilitated the development of eligibility criteria and reimbursement policies for this service (Grant et al. 2013), comparable to existing referral guidelines for inclusion in familial breast cancer screening programs linked to diagnostic algorithms incorporating BRCA mutation analysis (Schoeman et al. 2013). However, standardized eligibility criteria for inclusion in clinically orientated breast cancer risk management programs incorporating actionable low-penetrance genetic testing are currently lacking in the local setting. It is anticipated that our experience in cancer genetics will provide the basis for a similar envisioned venture positioned as a database for future oncogenomic research.
Preliminary findings gathered from a recent South African study (2014) which investigated 57 South African breast cancer patients and 125 population-matched controls have provided evidence supporting the clinical relevance of genetic testing considering low-penetrance polymorphic variants implicated in the dysfunctional regulation of catechol estrogen (CE) metabolism as pathogenic mechanism for sporadic breast cancer. Since the development of sporadic breast cancer is context-dependent, with genetic risk conferred by these variants subject to the risk-modulating activity of environmental exposures which trigger their expression, a multidisciplinary clinically orientated approach to the delivery of this genetic service is proposed. This approach may serve to identify a high-risk genetic subgroup of patients set to derive the greatest benefit from the timely implementation of lifestyle-centred harm reduction strategies aimed at decreasing cumulative risk for disease recurrence or associated comorbidities. The proposed research project aims to build on these findings and test the hypothesis that the polymorphic variants of interest not only confer risk at the individual level, but that their combined presence potentially constitutes a polygenic disease subtype associated with familial clustering of sporadic breast cancer not attributable to mutations in high-penetrance genes such as BRCA1 and BRCA2.
Insights gathered from such investigation may serve to validate the importance of clinical inquiry regarding family history in developing referral guidelines for genetic susceptibility testing, comparable to its established role in determining eligibility for high-penetrance genetic testing aimed at diagnosing or screening for certain Mendelian disorders. Given our experience in the field of breast cancer research, the development of the proposed prescreening eligibility algorithm will initially focus on this condition. However, comparable to the multifunctional pathogenic role of high-penetrance BRCA mutations in other lifestyle-related cancers, the importance of the proposed polymorphic variants of interest in other epithelial neoplasms provides the basis for latter extension to include coverage of other locally relevant cancers as well.