孟德尔随机化分析在结直肠癌血液标志物遗传背景研究中的应用

Application of Mendelian randomization analysis in investigating the genetic background of blood biomarkers for colorectal cancer

结直肠癌(colorectal cancer,CRC)是一种发生在结肠和直肠的消化道癌症,是全球第三常见癌症,也是癌症相关死亡的第二大原因。CRC的早期发现对于预防转移、降低死亡率、改善预后和提高患者生活质量至关重要。遗传因素在CRC的发生中扮演重要角色,可解释高达35%的疾病风险。全基因组关联研究已发现多个与CRC风险相关的遗传位点,但缺乏直接因果关系的证据。虽然传统的血液标志物如癌胚抗原(carcinoem-bryonic antigen,CEA)和糖类抗原19-9(CA19-9)已被广泛用于CRC诊断和监测,但在早期诊断应用中的灵敏度和准确性有限,仍需要开发新的能够反映遗传背景的生物标志物或其组合,以促进早期诊断和提高诊断准确性。同时,理解这些生物标志物的遗传机制对于揭示CRC的发病机制至关重要,并有助于开发更加精准的个体化治疗策略。孟德尔随机化(Mendelian randomization,MR)分析作为一种新兴的流行病学工具,通过减少观察性研究中存在的偏差问题,能够更精确地评估遗传变异与疾病间的因果关系。目前,MR分析已被用于评估多种血液标志物对CRC风险的因果影响,可更准确地表明血液标志物与CRC发病机制之间的潜在因果关系。本文综述了MR分析在CRC血液标志物研究中的应用,旨在为CRC的早期诊断和个体化治疗提供理论基础。

Colorectal cancer(CRC),a malignancy affecting the colon and rectum,ranks as the third most common cancer worldwide and the second leading cause of cancer-related deaths.Early detection of CRC is crucial for preventing metastasis,reducing mortality,improving prognosis,and enhancing patients’quality of life.Genetic factors play a significant role in CRC development,accounting for up to 35%of the disease risk.Genome-wide association studies have identified several genetic loci associated with CRC risk.However,these studies often lack direct evidence of causality.While traditional blood biomarkers such as carcinoembryonic antigen(CEA)and carbohydrate antigen 19-9(CA19-9)are widely used for CRC diagnosis and monitoring,their sensitivity and accuracy in early diagnosis are limited.Thus,there is a pressing need to develop new biomarkers that reflect the genetic background of CRC to improve early detection and diagnostic accuracy.In addition,understanding the genetic mechanisms underlying these biomarkers is essential for eluci-dating CRC pathogenesis and developing precise personalized treatment strategies.Mendelian randomization(MR)analysis,as an emerging epidemiological tool,can accurately assess the causal relationship between genetic variations and diseases by reducing confounding biases in observational studies.MR analysis has been applied in evaluating the causal impact of various blood biomarkers on CRC risk,shedding lights on the potential causal relationships between these biomarkers and CRC pathogenesis in the context of genetic background.In this review,we summarize the applications of MR analysis in studies of blood biomarkers for CRC,aiming to enhance the early diagnosis and personalized treatment of CRC.