Raising the age for starting colonoscopy to 35 years for individuals with path_MSH6 carriers may lead to missed opportunities for detecting advanced neoplasia in a notable percentage of carriers

INTRODUCTION:Recent guidelines for Lynch Syndrome recommend starting a colonoscopy at 30-35 years for path_MSH6 carriers. This study aimed to measure the rate of advanced neoplasia (AN) in these carriers up to age 35.METHODS:A multicenter retrospective analysis of endoscopic and pathological data for path_MSH6 carriers who underwent endoscopic surveillance at specialized high-risk clinics. Advanced colorectal neoplasia was defined as colorectal cancer (CRC) or advanced polyp (AP).RESULTS:The study included 197 participants from 141 unrelated families, 60.9% of whom were women, and 90.9% completed follow-up by the age of 35 years or reached the outcome. Eleven individuals (5.58%; 1/18) were diagnosed with AN at 35, with a median age of 29 (interquartile range: 26-31). Among these cases, six (3.05%) had AP and five (2.54%) were diagnosed with CRC. Among the CRC cases, one was classified as American Joint Committee on Cancer (AJCC) Stage I, three as Stage IIA, and one as Stage IV. Four of the 11 AN cases were detected through screening, accounting for 36.3% of AN cases and 2.03% of the total cohort (one of 50). This included one case of AJCC on Cancer stage I cancer and three cases of AP.DISCUSSION:Our findings suggest that the recommendation to raise the age for initiating colonoscopy to 35 years for path_MSH6 carriers merits careful consideration, as there is a possibility that AN may not be detected. Given the limited size of our study and the potential for ascertainment bias, we encourage further research to explore and validate our findings.