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

Abstract

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 elucidating 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.

Keywords: Mendelian randomization; biomarker; colorectal cancer; early diagnosis; genetics; instrumental variables.