Predictive Value of the PREMM5, MMRpredict Models, and the Universal Tumor Screening Strategy for Lynch Syndrome in Vietnam
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 572
- 试验地点
- 1
- 主要终点
- Predictive Value of PREMM5, MMRpredict, and Universal Tumor Screening for Lynch Syndrome in Colorectal Cancer Patients
研究概览
简要总结
This study evaluates the predictive value of PREMM5, MMRpredict models, and Universal Tumor Screening in detecting Lynch Syndrome in colorectal cancer (CRC) patients in Vietnam.
Vietnamese CRC patients (18-70 years) undergoing colonoscopy will be enrolled. Participants will complete a medical history questionnaire and provide blood samples for genetic testing. Tumor biopsy specimens will undergo Immunohistochemistry staining, BRAF V600E mutation, and MLH1 methylation analysis in case of loss of MLH1/PMS2 expression. Next-Generation Sequencing will detect germline MMR mutations, and biallelic somatic mutations will be analyzed if no germline mutations are found.
详细描述
- Background and Rationale Colorectal cancer (CRC) is one of the most prevalent malignancies worldwide and the second leading cause of cancer-related deaths. Approximately 5-6% of CRC cases are associated with hereditary cancer syndromes, with Lynch Syndrome (LS) being the most common. LS results from germline mutations in the Mismatch Repair (MMR) genes (MLH1, MSH2, MSH6, PMS2, and EPCAM), which lead to microsatellite instability (MSI) and an increased risk of CRC, endometrial, and other extracolonic malignancies.
Despite its significance, LS remains underdiagnosed, particularly in Asian populations, due to the limitations of traditional screening criteria, such as Amsterdam II and the Revised Bethesda Guidelines, which have low sensitivity in identifying LS patients. In response, universal tumor-based screening using MSI testing and immunohistochemistry (IHC) for MMR protein loss has been proposed as an effective alternative. Additionally, prediction models such as PREMM5 and MMRpredict have been developed to estimate LS risk based on clinical and family history.
However, these models and tumor screening strategies have not been validated in the Vietnamese population. This study aims to evaluate and compare the predictive performance of different screening approaches for LS in Vietnamese CRC patients, thereby optimizing genetic testing selection and early diagnosis. 2. Study Design and Setting
This is a cross-sectional study conducted at two major hospitals in Vietnam:
- University Medical Center at Ho Chi Minh City - GI Endoscopy Department
- Nguyen Tri Phuong Hospital - GI Endoscopy & Gastrointestinal Surgery Departments The study will enroll CRC patients aged 18-70 years who undergo colonoscopy with suspected tumors and are subsequently diagnosed with colorectal adenocarcinoma.
- Objectives
Primary Objective:
研究设计
- 研究类型
- Observational
- 观察模型
- Other
- 时间视角
- Cross Sectional
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged 18 to 70 years
- •Provide informed consent to participate in the study
- •Undergo colonoscopy with endoscopic findings suspicious for CRC
- •Have biopsy-confirmed adenocarcinoma through colonoscopic biopsy
排除标准
- •Active gastrointestinal bleeding
- •Currently using anticoagulants or antiplatelet agents
- •History of coagulation disorders or difficulty controlling bleeding
- •Incomplete colonoscopy to the cecum (excluding cases of tumor-induced obstruction)
结局指标
主要结局
Predictive Value of PREMM5, MMRpredict, and Universal Tumor Screening for Lynch Syndrome in Colorectal Cancer Patients
时间窗: At study completion (Month 24). The primary outcome will be analyzed after all participants have completed sample collection, genetic testing, and data processing, expected within 24 months from study initiation.
The study evaluates the diagnostic accuracy of PREMM5, MMRpredict models, and Universal Tumor Screening (IHC testing) in detecting Lynch Syndrome (LS) in colorectal cancer (CRC) patients. The outcome will be assessed by calculating sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the receiver operating characteristic curve (AUC-ROC) for each screening method compared to gold-standard germline MMR gene mutation testing (via Next-Generation Sequencing - NGS).
次要结局
- Prevalence of Lynch Syndrome in Colorectal Cancer Patients(At study completion (Month 24))
- Clinical Characteristics of Lynch Syndrome-Associated CRC(At study completion (Month 24))
- Endoscopic and histopathological features of Lynch Syndrome-Associated CRC(At study completion (Month 24))
- Comparison of Screening Criteria and Prediction Models for Lynch Syndrome(At study completion (Month 24))
研究者
Doan Thi Nha Nguyen
Principal Investigator
University of Medicine and Pharmacy at Ho Chi Minh City