Genetic Cancer Susceptibility Group
The main objective of GCS′s research interests is to investigate the influence of genetic variation on cancer etiology: to identify the genes involved, the mechanisms by which genetic variants exert their effect, and how they interact with environmental factors. To achieve this, GCS scientists with backgrounds in genetics, genomics, bioinformatics, and pathology work together to develop innovative genomics-based study designs. The objective of GCS is therefore to develop multidisciplinary genomic applications, including:
- Laboratory. Optimization of laboratory workflows and quality control procedures for the particular setting of samples collected across a variety of settings.
- Pathology. Ensuring appropriate morphological review, adapting sampling methods to ensure that the relevant tissue types are available for study, and making the link between morphological and molecular features.
- Computational science. Developing and implementing the bioinformatics resources required for the analysis of the genomics data. GCS develops methods that enable the integration of these multi-layered genomics data and, ideally, augment the more traditional analysis approaches.
GCS then applies these methods in epidemiological studies, particularly within large international consortia. An example is GCS′s recent work in the lung cancer OncoArray project as part of the Genetic Associations and Mechanisms in Oncology (GAME-ON) initiative. First, GCS used its genetics and bioinformatics skills to harmonize, combine, and analyse very large genetic datasets across multiple studies. Second, GCS used its laboratory skills to confirm the veracity of the findings arising from this first analysis by confirming the fidelity of genotyping results. Finally, GCS explored the functional effects by using genomic measures to determine the functional effects of these genetic variants.
GCS continues to undertake this type of study but also focuses on the genomic analysis of exceptional samples identified within these large studies; examples are patients who have inherited susceptibility alleles, nasopharyngeal cancers that arise in patients who have consumed large amounts of salted fish in South-East Asia, and multi-omics studies of very rare lung neuroendocrine neoplasms and mesothelioma collected across multicentre studies.
The other major objective of GCS is the Group′s responsibilities regarding genomics at the Agency. Here, the focus is on the adaptation of genomic techniques to suit IARC′s particular needs and mission, while ensuring their optimal application and cost-effectiveness. These techniques are applied in GCS′s research and, through the Genetics Platform (GSP), also in scientific activities across IARC. The GSP makes these genomic techniques accessible to IARC scientific groups and provides support throughout the complete project life-cycle, including planning, execution, quality control, and subsequent analysis. Working closely with various IARC committees (Laboratory Steering Committee [LSC] and Computational Biology, Bioinformatics, and Biostatistics [C3B] Steering Committee) and scientific groups, GCS also coordinates the development of the Agency′s genomic and bioinformatics capacity and provides training at IARC and elsewhere, in these areas.