Section of Genetics - Genetic Cancer Susceptibility Group
Current Research Topics:
The areas of GCS′s studies on lung cancer, head and neck (including nasopharyngeal) cancer, and lymphomas include:
Investigating the contribution of germline genetic variation to cancer susceptibility, particularly uncommon genetic variants assessed by next-generation sequencing and genome-wide association study (GWAS) approaches. Findings are validated and explored using larger-scale targeted sequencing in cases and controls selected within bio-repositories in the Section of Genetics (GEN) (focused on selected genes in many individuals), or through imputation techniques within the large GWAS resources available to GEN. Examples of GCS activities include:
- Identifying the BRCA2 genetic variant rs11571833 (K3326X) to be associated with lung cancer (Wang et al., Nat Genetics 2014)
- Identifying that genetic variation in the TCF3 gene is linked with Hodgkin lymphoma, and potentially through alterations in gene expression levels (expression quantitative trait loci [eQTLs]) (Cozen et al., Nat Commun 2014)
- Identifying RINK1 as a potential breast cancer susceptibility gene (Park et al., Cancer Discovery 2014).
Exploring how genetic susceptibility may be mediated by considering how susceptibility alleles relate to gene expression levels and number or types of somatic mutations (mutation signatures and their dosage). In addition, GCS explores novel analytical methods to assess whether the identification of somatic events could further enhance susceptibility gene discovery, particularly in rare cancers, by considering unexpected correlations between somatic and germline events. Recent examples of GCS activities include:
- Identifying that genetic variants that are eQTLs are enriched for association with Hodgkin lymphoma (Cozen et al., Nat Commun 2014)
- Developing Bayesian methods that allow data integration into genetic studies (Johansson et al., PLoS One 2012).
Investigating genetic susceptibility to nasopharyngeal cancer within the South-East Asian population, including interactions with environmental exposures, Epstein-Barr virus, and tumour biology across populations and ethnicities.
- Identifying genetic variants in TERT to be linked with nasopharyngeal cancer (Fachiroh et al., Cancer Causes Control 2012).
- Although the Group′s primary focus is on genetic susceptibility, most recently GCS is exploring and developing laboratory and bioinformatics analysis protocols, for the evaluation of novel non-invasive biomarkers for early diagnosis of cancer, such as circulating tumour DNA or exosomal RNAs from plasma samples.