P2141 - Differences in Lynch Syndrome Surveillance Colonoscopy by Mismatch Repair Gene Type: Experiences From a Mid-Atlantic Healthcare System

Joseph Atarere, MD, MPH¹, Boniface Mensah, MBChB, MPH¹, Mariah Malak Bilalaga, MD¹, Ramya Vasireddy, MBBS¹, Ted Akhiwu, MBBS, MPH¹, Greeshma Gaddipati, MBBS¹, Simardeep Singh, MBBS¹, Stephanie M. Woo, MD², Priyanka Kanth, MD^2
1MedStar Union Memorial Hospital, Baltimore, MD; ²MedStar Georgetown University Hospital, Washington, DC

Introduction: Lynch syndrome (LS) is caused by germline mutations in the mismatch repair (MMR) system. Mutations in MLH1 and MSH2 account for 70%-90% of LS and carriers have the highest risk of developing colorectal cancer (CRC). Screening colonoscopies are recommended for all individuals with LS starting at age 20- 25, with considerations to begin at ages 30 and 35 years in those with MSH6 and PMS2 respectively. Current guidelines recommend follow-up colonoscopies every 1-2 years, regardless of MMR gene type. In this study, we compared the time from baseline colonoscopy to detection of a high-risk lesion or CRC to determine if a different follow-up schedule may be appropriate for certain MMR types.

Methods: We extracted data from a retrospective cohort of patients with a germline diagnosis of LS who received colonoscopies between April 13^th, 2005, and February 27^th, 2024. Only those with normal baseline colonoscopy findings were included. We had a composite outcome of CRC or high-risk lesion [adenoma, sessile serrated polyp (SSP)] detection on follow-up colonoscopies. The primary independent variable was germline mutation (MLH1, MSH2, MSH6, PMS2 and EPCAM). We plotted Kaplan-Meier (KM) survival curves for the length of time from baseline colonoscopy till study outcome occurrence by MMR subtype, comparing the survivor functions with log-rank tests. We described the relationship between MMR subtype and time to study endpoint using an age and sex-adjusted cox-proportional hazard model.

Results: We included a total of 96 patients in this study of which 22 (22.9%) had MLH1 mutations. Most (80.2%) of the population were female and the mean number of colonoscopies was 3. The average duration of follow-up was highest for MSH2 (64 months) and lowest for PMS2 (24 months) (Table 1). The age-adjusted KM survival showed a significant difference in time to study outcome by mutation type (p = 0.045) (fig 1). In the adjusted cox-proportional hazard model, compared to MLH1, there was no difference in the detection of adenoma, SSP or CRC among patients with MSH2, MSH6, and PMS2 mutations.

Discussion: Patients with MSH2 and MLH1 had the longest duration of follow-up which is reassuring as they have the highest risk of developing CRC. Interestingly, no differences were noted in the development of precancerous lesions and CRC between MMR subtypes.



Disclosures:


Joseph Atarere, MD, MPH¹, Boniface Mensah, MBChB, MPH¹, Mariah Malak Bilalaga, MD¹, Ramya Vasireddy, MBBS¹, Ted Akhiwu, MBBS, MPH¹, Greeshma Gaddipati, MBBS¹, Simardeep Singh, MBBS¹, Stephanie M. Woo, MD², Priyanka Kanth, MD². P2141 - Differences in Lynch Syndrome Surveillance Colonoscopy by Mismatch Repair Gene Type: Experiences From a Mid-Atlantic Healthcare System, ACG 2024 Annual Scientific Meeting Abstracts. Philadelphia, PA: American College of Gastroenterology.