DYNAMICS-LYNCH：DNA Methylation Analysis in Stool for Screening of Lynch Syndrome-Associated Colorectal Cancer

Colorectal cancer (CRC) has high incidence and mortality rates globally. Over 1 million new cases are diagnosed annually, and about 600,000 people die from the disease each year. In China, CRC ranks third in incidence and fifth in mortality. Its rates are rising due to lifestyle changes and an aging population. Around 30% of CRC cases have a hereditary component, including familial adenomatous polyposis (FAP) and Lynch syndrome. Lynch syndrome, or hereditary non-polyposis colorectal cancer (HNPCC), accounts for 3%-5% of CRC cases. Early diagnosis, screening, and prophylactic surgery can reduce CRC mortality by 7%-42%, and mortality from endometrial and ovarian cancers by 1%-6%. Intensive screening is essential for Lynch syndrome patients, who are at high risk for CRC. Due to the lack of early symptoms, many CRC cases are diagnosed in later stages, causing financial strain on patients, families, and society. Screening is an effective tool in reducing CRC-related mortality by more than 50%. In developed countries such as the U.S., U.K., and Japan, CRC screening is integrated into public health programs, emphasizing its role in prevention. In China, CRC screening mainly involves the fecal occult blood test followed by colonoscopy, but this method faces challenges. First, the fecal occult blood test lacks sufficient sensitivity, leading to underdiagnosis. Second, colonoscopy is invasive with low patient acceptance. It also requires specialized facilities, advanced equipment, and skilled endoscopists, limiting its accessibility. Given China's large population and limited healthcare resources, universal colonoscopy screening is challenging, resulting in low screening rates. To address these challenges, we propose replacing part of colonoscopy screening with DNA methylation testing of fecal samples. Self-sampling methylation screening could ease the strain on healthcare resources and improve patient compliance. By combining methylation screening with colonoscopy, we aim to reduce colonoscopy frequency and enhance overall compliance. This study will include three rounds of methylation screening with colonoscopy as the control, involving 400 Lynch syndrome patients. The goal is to develop new screening criteria for this high-risk group, reduce colonoscopy frequency, and ultimately lower CRC incidence in Lynch syndrome patients.

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Inclusion Criteria:

* Informed consent: patients are required to participate voluntarily and sign an informed consent form in writing；Patients diagnosed with Lynch syndrome；Agree to collect and send stool specimens for methylation sequencing as required；Willingness to undergo long-term follow-up and three rounds of methylation screening

Exclusion Criteria:

* Patients with confirmed familial adenomatous polyposis or other hereditary colorectal cancers that are not Lynch syndrome；Patients who are unable to obtain a fecal specimen or whose specimen is substandard for follow-up testing；Patients diagnosed with colorectal cancer or currently undergoing surgery；Failure to sign informed consent