International Mismatch Repair Consortium

Project Details

Lynch syndrome is a familial cancer syndrome caused by inherited mutations in the mismatch repair genes: MLH1, MSH2, MSH6 and PMS2, and the EPCAM gene. Mutation carriers are at increased risks of cancers of the bowel, uterus and several other sites; however, current estimates of cancer risks (penetrance) for specific mutation carriers are limited for clinical translation. Our vision is to collect and analyse Lynch syndrome families (a genetic predisposition to cancer), contributed by a very large worldwide consortium, to provide the most accurate and precise, person-specific estimates of cancer risk.

Aim 1:

Establishment of data set: We will obtain pedigree data for over 8,800 Lynch syndrome families contributed by the International Mismatch Repair Consortium that we established.

Aim 2:

Penetrance of mismatch repair gene mutations: We will estimate the age-specific cumulative risk (penetrance) of cancers at each anatomical site for Lynch syndrome by: sex; mismatch repair gene; type and location of mutation; and the geographic region of the mutation carrier.

Aim 3:

Personal cancer risk tool: We will develop a clinical tool to calculate the 10-year risks of cancer for people with Lynch syndrome based on their age, sex, gene mutated, type of mutation and geographic region.

Project summary

The International Mismatch Repair Consortium (IMRC) is a world wide collaboration of over 115 investigators from 59 centres/clinics in Africa, Asia, Australasia, Europe, North and South America, all of whom provide clinical care and/or conduct research on Lynch syndrome families. This consortium has been established by Professors Jenkins, Macrae and Haile drawing on the major groups in the world facilitated by the International Society for Gastrointestinal Hereditary Tumours (InSiGHT) and by the Collaborative Group of the Americas on Inherited Colorectal Cancer (CGA). Collectively, the IMRC will have the pedigree data for over 8,800 Lynch syndrome families including over 20,000 known carriers of a germline mutation in a mismatch repair gene.

Researchers

Professor Mark Jenkins

Professor Finlay Macrae (Royal Melbourne Hospital Academic Centre, Melbourne Medical School, The University of Melbourne)

Professor Ingrid Winship (Melbourne Health)

Dr Aung Ko Win

Dr James Dowty

Dr Robert Haile (Stanford University)

Funding

NHMRC

Research Group

Colorectal Cancer



Faculty Research Themes

Cancer

School Research Themes

Prevention and management of non-communicable diseases (including cancer), and promotion of mental health, Screening and early detection of disease



Key Contact

For further information about this research, please contact the research group leader.

Department / Centre

Centre for Epidemiology and Biostatistics