OR15: Worldwide study of cancer risks for Lynch syndrome: International mismatch repair consortium (IMRC)

Mark Jenkins1, Aung Win1, Jeanette Reece1, Grant Lee1, Allyson Templeton2, Robert Haile3, Gabriela Moslein4, Finlay Macrae5 for the IMRC.

1. Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health The University of Melbourne, Parkville, Victoria, Australia. 2. Fred Hutchinson Cancer Research Center, USA. 3. School of Medicine, Division of Oncology, Stanford University. 4. HELIOS St. Josefs-Hospital Bochum-Linden, Germany. 5. Department of Medicine, The University of Melbourne, Parkville, Victoria, Australia


To bridge critical gaps in Lynch syndrome research, the International Mismatch Repair Consortium (IMRC) was formed in 2010. The IMRC comprises major worldwide consortiums involved in the research and/or clinical treatment of Lynch syndrome (cancer predisposition caused by inherited mutations in mismatch repair (MMR) genes: MLH1, MSH2, MSH6, PMS2 and EPCAM); http://www.sphinx.org.au/imrc. The establishment of the IMRC was facilitated by the International Society for Gastrointestinal Hereditary Tumours (InSiGHT) and the Collaborative Group of the Americas on Inherited Colorectal Cancer (CGA). Currently, the IMRC has 205 members from 74 centres/clinics in Africa, Australasia, Europe, North and South America, and membership is open to anyone involved in research related to Lynch syndrome and/or the treatment of Lynch syndrome families.

Accurate cancer risk estimates are needed to develop genetic counselling guidelines, and are of importance for the clinical management of mutation carriers and members within high-risk families. Risk may differ not only by age and gender and the gene that is mutated, but also by the country, and ethnicity of the carrier.  The only way to thoroughly address this potential heterogeneity is to conduct comprehensive penetrance analyses on large, ethnically heterogeneous samples of persons/families segregating mutations in MMR genes.


The IMRC will: (i) establish a combined data set of pedigree data from around the world for approximately 8,800 Lynch syndrome families; (ii) estimate the age-specific cumulative risk (penetrance) of cancers at each anatomical site by sex, mismatch repair gene, type of mutation, and nationality/geographic region; and (iii) develop a personal risk tool for clinical use that provides 10-year risks of cancer based on the age, sex, mismatch repair gene, type of mutation, and nationality/geographic region.


Since July 2014, IMRC investigators from 63 sites were contacted and requested to submit the MMR family data from their clinics/centres. Instructions on the preferred data format were provided, including data dictionaries for personal and family history of demographic data, cancers, MMR gene mutation status, screening, surgery and mortality.  As of April 2016, 28 investigators representing 38 sites of 18 countries have submitted MMR pedigree data for 4302 families including 11418 mutation carriers.

Families 1401 1807 669 388 37 4302
Carriers 3657 4878 1922 836 125 11418

For many of the sites contacted, the required data for this analysis is not in electronic form and requires manual data entry at the site. Data checking and recontacting contributors for clarification is underway.


Collection of MMR family data from many international sites, with varying resources (many of which were not established or designed for epidemiological research) is challenging.  The IMRC will be investigating ways to facilitate data collection for this project to ensure the maximum benefit is gained from this collegial and international consortium.

Funding source: Australian National Health and Medical Research Council.