Key projects

Identifying novel genetic risk factors for Colorectal Cancer across the spectrum of risk, from high- to low-penetrance variants, through the use of whole genome and whole exome sequencing in families with multiple CRC-affected individuals (Familial Colorectal Cancer Type X) and through case-control genome-wide association studies (GWAS).

Improving our understanding of Lynch Syndrome, that is, individuals who carry a high-risk mutation in one of the DNA mismatch repair (MMR) genes. Our research focuses on the identification of individuals with a MMR gene mutation in the population, investigating potential genetic and environmental modifiers for CRC development and exploring the diagnostic utility of testing for MMR function in CRC, endometrial cancer as well as other cancers not typically associated with the syndrome. We continue to work collaboratively towards classifying MMR gene variants of uncertain clinical significance and have active projects investigating the clinically significant group of families who have “suspected” or “Lynch-like” syndrome, that is, individuals have tumours demonstrating MMR-deficiency but a causative germline mutation cannot be identified.

We continue to work with the community organisation Lynch Syndrome Australia to aid in the transfer of research findings to consumers.

Understanding the aetiology of Serrated Polyposis Syndrome (SPS). Using the largest resource of individuals with Serrated Polyposis Syndrome (SPS) and their relatives collected to date, we have contributed to a greater understanding of the SPS phenotype and the molecular pathology features of polyps and CRCs in SPS patients. We continue to develop evidence for the genetic predisposition to SPS, having shown that relatives of individuals with SPS have an increased risk of developing CRC. We have also demonstrated that genetic mutations in the known CRC- and polyposis-predisposing genes BMPR1A, SMAD4, PTEN, MUTYH and GREM1 do not commonly underlie SPS. Our research is focused on utilising whole genome and whole exome sequencing to identify genetic risk factors for SPS.

Identifying biomarkers of risk and poor prognosis in CRC including:

1. peripheral blood biomarkers that indicate or quantify an individual's risk for developing CRC or other cancers; specifically, testing for risk associated SNPs and/or measuring DNA methylation of white blood cell DNA as a marker of cancer risk
2. tumour biomarkers that indicate that a relative may be at an increased risk of developing CRC
3. tumour features that are associated with a poor prognosis.