Nadine Abu-Ghazaleh 1,2, Varun Kaushik 1,2, Alexandra Gorelik 2,3, John Paul Plazzer 1,2, Prof Mark Jenkins Prof. 1,4, Prof. Finlay Macrae 1,2

1Department of Medicine, University of Melbourne, Melbourne, Australia, 2Department of Colorectal Cancer and Genetics, Royal Melbourne Hospital, Melbourne, Australia, 3Monash Department of Clinical Epidemiology, Cabrini Institute, Melbourne, Australia, 4School of Population and Global Health, University of Melbourne, Melbourne, Australia

Background/Aims: Lynch Syndrome (LS) is the most common hereditary colorectal cancer (CRC) syndrome with an estimated prevalence of 2-3% of CRC. The screening for LS has varied considerably across different studies which has led to wide estimates of prevalence of LS. A prevalence study is needed to provide healthcare leaders with an accurate estimate of the true prevalence of LS. Establishing robust prevalence estimates in different populations will inform workforce and colonoscopy provision planning and develop optimal strategies for effective detection and preventative actions.

Methods: In this study, we perform a systematic review to identify the global prevalence of LS in CRC patients as well as assess multiple parameters that influence the prevalence of LS. These include age, ethnicity, intervention and diagnostic strategy, and subject setting selection. MEDLINE (Ovid) and Embase were searched for all studies that involved screening for LS using germline testing and two reviewers reviewed full text articles and extracted data independently. To our knowledge, this is the first systematic review and meta-analysis of the worldwide prevalence of LS in CRC.

Results: A total of 3,575 studies were identified and after the review process 35 studies were include in this review. The overall pooled yield of LS screening was 3.0% (95%CI 2-3%). Studies performing germline tests on all CRC participants reported higher prevalence (5.0%) as opposed to studies only performing germline test on participants with tumors with MMR deficiency (3.0%) or MSI (2.0%).

Conclusion: Prevalence of LS across multiple ethnic, geographic and clinical populations is remarkably similar. Direct germline testing of patients presenting with cancer identifies more LS carriers than those based on two stage testing. Young patients presenting with CRC and those with an Amsterdam positive family history provide the highest returns for LS identification.

Keywords: Lynch Syndrome (LS), Colorectal Cancer, Worldwide prevalence