Aung Ko Win

Photo of Aung Ko WinCentre for Epidemiology and Biostatics, The Melbourne School of Population and Global Health, The University of Melbourne, Victoria, Australia

Role of environmental modifiers in the risk of colorectal cancer for Lynch syndrome

on behalf of the Colon Cancer Family Registry investigators

People with germline mutations in DNA mismatch repair (MMR) genes have a substantially elevated risk of colorectal cancer (known as Lynch syndrome), but the modifiers of this risk are not well established. Identifying modifiers of cancer risk is important for understanding carcinogenesis as well as for genetic counselling, screening, and risk-reduction strategies. We conducted a study using 1,992 (1,126 female) mutation carriers from the Colon Cancer Family Registry. We found that intake of aspirin, ibuprofen, multivitamin supplements, calcium supplements, oestrogen and progestin hormone therapy use, hormonal contraceptive use, and being parous are associated with a decreased risk of colorectal cancer while increased body mass and alcohol consumption are associated with an increased risk. Environmental factors are important modifiers of the risk of colorectal cancer in Lynch syndrome.

Potential of International Mismatch Repair Consortium (IMRC) collaboration

on behalf of the IMRC investigators

Risk of colorectal and other cancers in Lynch syndrome may vary by ethnicity and by country due to geographical or cultural differences in the prevalence of modifiers and/or geographical or ethnic differences in the mismatch repair mutations. However, to date almost all the estimates on cancer penetrance are from studies in which the vast majority of mutation carriers are Caucasian in Western environments. The only way to address this problem is to conduct comprehensive penetrance analyses on large, ethnically heterogeneous samples of persons/families segregating mutations in mismatch repair genes. The International Mismatch Repair Consortium (IMRC) was formed in 2010 and comprises the major research and clinical groups in the world researching and treating Lynch syndrome throughout Africa, Asia, Australasia, Europe, North and South America. We are now collecting family pedigree and cancer data from participating members to refine the penetrance of cancers for Lynch syndrome. As an example of the potential of the IMRC, I will compare new penetrance estimates from two ethnically diverse IMRC sites, Germany and Hong Kong.