Cutting-edge research employing Mendelian randomization analysis has uncovered significant associations between immune-related gene expression and colorectal cancer (CRC) risk. These findings offer new perspectives on the genetic mechanisms underlying CRC and carry promising clinical implications for risk assessment and targeted intervention strategies.
The investigation of immune-related gene expression is rapidly advancing at the intersection of oncology and genomics. Clinicians and researchers are increasingly leveraging high-throughput genetic tools to understand cancer susceptibility and guide precision medicine. Recent discoveries in this space do more than clarify risk—they reveal genetically validated targets that may one day support individualized therapies.
Immune Gene Expression as a Driver of Cancer Risk
Variation in immune-related gene expression is emerging as a key regulator of immune system function and cancer vulnerability. Alterations in the expression of genes that govern immune cell activity can modify the host’s ability to detect and eliminate malignancies, thereby shaping susceptibility to colorectal cancer.
A recent study published in Discover Oncology demonstrated that decreased expression of the FHL3 gene—a gene involved in immune regulation—was associated with an increased risk of CRC. Lower FHL3 expression also correlated with worse survival outcomes in CRC patients, highlighting its potential as both a prognostic biomarker and therapeutic target (Tan et al., 2025).
Mendelian Randomization: A Tool to Infer Causality
Mendelian randomization (MR) analysis leverages genetic variants—typically single nucleotide polymorphisms (SNPs)—as instrumental variables to test causal relationships between exposures (such as gene expression) and disease outcomes. This approach helps minimize confounding and reverse causation, challenges that often undermine observational studies.
The Discover Oncology study utilized cis-expression quantitative trait loci (cis-eQTL) data across various immune cell types to perform MR analyses. Genetic data from over 78,000 CRC cases and 107,000 controls of European ancestry were used to strengthen causal inference and statistical power (Tan et al., 2025).
Complementing these findings, another investigation published in BMC Cancer applied a bidirectional, two-sample MR design to explore causal links between 731 immune cell traits and CRC risk. The study employed inverse-variance weighted methods and corroborated the hypothesis that immune phenotypes exert a directional influence on colorectal carcinogenesis (Liu et al., 2025).
Clinical Implications and Next Steps
The convergence of data from multiple MR studies supports the idea that immune gene dysregulation is not merely a consequence of cancer but a potential contributing cause. These findings lay the groundwork for incorporating genetic markers—such as FHL3 expression levels—into early screening frameworks and personalized treatment regimens.
Furthermore, the association between gene expression and both CRC risk and patient survival underscores the dual utility of certain immune genes as diagnostic and prognostic tools. As precision oncology evolves, such insights could drive the development of immune-modulatory therapies tailored to a patient’s genetic profile.
Still, there is an urgent need to expand this research across more diverse populations and conduct functional assays to validate these genetic targets. Population-specific gene expression patterns may differ, and broadening the genomic dataset is essential to ensure equitable clinical translation.
For healthcare providers and oncology researchers, these discoveries reinforce the value of genetic literacy and interdisciplinary collaboration. As the field advances, integrating molecular epidemiology into clinical decision-making will become increasingly central to optimizing colorectal cancer care.