Cancer Genetics and Epigenetics, 2025, Vol.13, No.1, 1-10 http://medscipublisher.com/index.php/cge 1 Review Article Open Access Advances in Genetic Susceptibility Studies of Colorectal Cancer: From Single Genes to Polygenic Huixian Li, Jianhui Li Institute of Life Science, Jiyang College of Zhejiang A&F University, Zhuji, 311800, Zhejiang, China Corresponding author: jianhui.li@jicat.org Cancer Genetics and Epigenetics, 2025, Vol.13, No.1 doi: 10.5376/cge.2025.13.0001 Received: 07 Nov., 2024 Accepted: 18 Dec., 2024 Published: 02 Jan., 2025 Copyright © 2025 Li and Li, This is an open access article published under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Preferred citation for this article: Li H.X., and Li J.H., 2025, Advances in genetic susceptibility studies of colorectal cancer: from single genes to polygenic, Cancer Genetics and Epigenetics, 13(1): 1-10 (doi: 10.5376/cge.2025.13.0001) Abstract This study analyzed the genetic causes of Colorectal cancer (CRC), a disease influenced by multiple factors, in which the role of genetic factors accounted for approximately 35%. The research focuses on the changes in the research direction of this field. In the early stage, it mainly studied single-gene high-penetrance mutations (such as APC and mismatch repair genes), but now it has shifted to studying complex risk situations involving medium-risk variations and a large number of low-penetrance polymorphisms. By studying more than 200 common risk loci identified in genome-wide association studies (GWAS). This study explains how the polygenic Risk Score (PRS) classifies an individual's risk of disease beyond traditional family medical history, also discussed the important role of the research method combining multiple omics such as transcriptomics, epigenomics and microbiomics in deeply understanding the biological pathways of CRC susceptibility and improving the accuracy of risk prediction models. Although there have been many achievements, this study also analyzed the current difficulties encountered in functional verification, applicable population range and clinical application. Finally, this study points out that to achieve breakthroughs in the future, it is necessary to collaborate among different disciplines, increase data on different populations, and integrate artificial intelligence technology. Only in this way can the role of personalized prevention and screening of CRC be fully exerted. Keywords Colorectal cancer (CRC); Genetic susceptibility; Polygenic risk score (PRS); Genome-wide association studies (GWAS); Multi-omics integration 1 Introduction Colorectal cancer (CRC) is a major global health problem and one of the most prevalent types of cancer worldwide, exerting significant pressure on public health efforts, especially in Westernized countries (Lorans et al., 2018). It is estimated that approximately 35% of colorectal cancer cases are related to genetic factors, while high-risk mutations that cause known susceptibility genes such as Lynch syndrome and familial adenomatous polyposis account for 5%~10% of the cases (Pearlman et al., 2017; Lorans et al., 2018). It should be particularly noted that many patients with early-onset colorectal cancer carry pathogenic germline mutations in their bodies. This reflects the key role of genetic factors in the risk of colorectal cancer and also indicates the importance of genetic testing for formulating effective prevention and control strategies (Pearlman et al., 2017; Yurgelun et al., 2017). When the genetic susceptibility of colorectal cancer was initially studied, the main focus was on high penetrance mutations of single genes, such as mismatch repair genes and APCgenes, which were associated with distinctive genetic syndromes (Chubb et al., 2015; Pearlman et al., 2017; Lorans et al., 2018). Later, the emergence of multi-gene detection technology expanded the scope of research and enabled the detection of high and medium penetrance mutations in more genes (Yurgelun et al., 2017; Pearlman et al., 2017; Lorans et al., 2018). Recently, through genome-wide association studies (GWAS) and multi-omics research methods, more than 200 common genetic variations related to the risk of colorectal cancer have been discovered. Many variations are in non-coding regions and jointly constitute the multi-gene risk status of colorectal cancer (Schmit et al., 2018; Guo et al., 2020; Yuan et al., 2021; Chen et al., 2023; Chen et al., 2024). The polygenic risk score, which integrates the effects of multiple common variations, can now identify the population with a significantly increased risk of colorectal cancer (Schmit et al., 2018; Chen et al., 2024).
RkJQdWJsaXNoZXIy MjQ4ODYzNA==