Precision prevention and early detection of colorectal cancer in Lynch syndrome

Summary This project aims to establish a personalised risk prediction tool of colorectal cancer for people with Lynch syndrome by incorporating all known risk factors (genetic, environmental, personal and family history) to enable risk-based screening and preventive strategies, with the ultimate aim to reduce Lynch syndrome burden across Australia and worldwide.

Project Details

About 10% of colorectal cancers diagnosed before age 50 are due to Lynch syndrome, a familial cancer syndrome caused by inherited mutations in the DNA mismatch repair genes MLH1, MSH2, MSH6 and PMS2, or EPCAM. Approximately 1 in 280 people in the Western population have Lynch syndrome; predicting about 89,000 in Australia alone and 27 million worldwide who are at greatly increased risk of cancers. People with Lynch syndrome have substantially increased risks of colorectal cancer and many other cancers. On average, about a third to one-half are likely to be diagnosed with colorectal cancer by age 70, so carriers are recommended to screen 1-2 yearly colonoscopy.

All carriers are not at the same level of risk. There is a wide variation (risks to age 70 range from 0 to 100%). However, it is not currently possible to distinguish those at high risk from those at low risk. Therefore, clinicians can only recommend screening and preventive measures for Lynch syndrome carriers only based on the average risk (30-50% risk), which in fact is the least likely. Consequently, people at high risk are prescribed inadequate care (and therefore remain at increased risk of the disease) and people at low risk are prescribed excessive care (and therefore subject to unwarranted expensive and potentially risky invasive colonoscopy).

This project aims to provide a personalised risk assessment tool by utilising biospecimens (blood), baseline data (cancer, clinical, pathology, epidemiology) and follow-up data (incidence, mortality) of over 2,300 carriers from the Colon Cancer Family Registry, which have been already has been completed and funded by the NIH.