N09: Worldwide Study Of Cancer Risks For Lynch Syndrome: International Mismatch Repair Consortium (IMRC)

M. Jenkins1, J.C. Reece1, G. Lee1, R. Haile2, G. Moslein3, F. Macrae4, A. Win1

1 – University of Melbourne, Australia, 2 – Cedars-Sinai Medical Center, USA, 3 – Helios St. Josefs-Hospital Bochum-Linden, Germany. 4 – Royal Melbourne Hospital.


Aim: The International Mismatch Repair Consortium (IMRC) was established to determine cancer risks by geographic region.

Method: Pedigree data for 6,436 Lynch syndrome families from 22 countries were submitted by researchers/clinicians throughout the world to the analysis team at the University of Melbourne. We estimated the cumulative risks (penetrance) by geographic region.  We used a modified segregation analysis and adjusted for any ascertainment of families.

Results: Preliminary analysis suggest that for MLH1 mutations, the risk of colorectal cancer to age 70 is highest for carriers in Australasia (68% males, 55% females) and North America (61% males, 48% females) and lowest for carriers in South America (12% males, 10% females) and East Asia (20% males, 14% females).  For MSH2, the patterns were similar, except for South America which had a high estimated average risk (82% males, 75% females).

Conclusion: Collection of MMR family data from many international sites has progressed well despite the challenges faces by sites to establish databases for epidemiological research with varying resources. Preliminary results suggest that cancer risks for people with Lynch syndrome differ by geographic region which is consistent with environmental modifiers for the disease and might justify region specific screening guidelines.