Glucose Homeostasis and Shared Genetic Factors in Colorectal Cancer

Genetic and Molecular Insights Into Glucose Homeostasis and Colorectal Cancer: Exploring Pleiotropic Genes and Mechanistic Roles in Colorectal Cancer Patients

Colorectal cancer (CRC) and diabetes mellitus are two common diseases that frequently occur together and may share underlying genetic, metabolic, and immune-related mechanisms. Previous studies have shown that diabetes is associated with an increased risk of colorectal cancer and poorer clinical outcomes, while colorectal cancer itself may also influence glucose metabolism.

This prospective observational study aims to investigate the relationships among glucose homeostasis, shared genetic factors, inflammatory responses, immune cell profiles, and colorectal cancer outcomes. Participants with colorectal cancer and non-colorectal cancer controls will undergo serial assessments of glucose-related biomarkers, inflammatory markers, immune cell populations, and genetic analyses over time.

The study will focus on identifying shared genetic variants that may contribute to both colorectal cancer and diabetes-related traits, as well as exploring biological pathways involving inflammation, immune regulation, and metabolism. Blood samples and available colorectal tissue specimens will be analyzed to evaluate gene expression, immune cell distribution, and molecular changes associated with disease progression.

The results of this study may improve understanding of the biological links between colorectal cancer and diabetes, facilitate the development of personalized risk assessment strategies, and identify potential biomarkers and therapeutic targets for patients with colorectal cancer.

Colorectal cancer (CRC) and diabetes mellitus (DM) are major public health challenges worldwide. Epidemiological studies have demonstrated a bidirectional association between these two diseases, suggesting the existence of shared biological mechanisms involving glucose regulation, inflammation, immunity, and genetic susceptibility. However, the genetic and molecular pathways linking CRC and abnormal glucose homeostasis remain incompletely understood.

Recent genomic studies have identified several candidate pleiotropic genes that may influence both glycemic traits and CRC risk. Among these candidates, SMAD7 has emerged as a potential shared genetic factor involved in glucose homeostasis, inflammatory signaling, immune regulation, and colorectal tumorigenesis. SMAD7 participates in the TGF-β and NF-κB signaling pathways and may influence interactions between metabolic dysregulation, chronic inflammation, and cancer progression.

The present study is designed to investigate the genetic, molecular, metabolic, and immunological relationships between CRC and glucose homeostasis abnormalities. Large-scale genomic resources and clinical data will be integrated to identify and validate shared genetic variants associated with both conditions. In addition, a prospective observational cohort will be established to evaluate longitudinal changes in glucose metabolism, inflammatory biomarkers, immune cell profiles, and gene expression patterns in patients with CRC.

Particular emphasis will be placed on the characterization of systemic and tumor-associated immune responses, including cytotoxic T lymphocytes and regulatory T cells, and their relationships with glucose homeostasis and candidate genetic variants. Blood samples and available colorectal tissue specimens will be analyzed using molecular, genomic, and immunologic approaches to explore potential mechanisms linking metabolic abnormalities and colorectal cancer progression.

By integrating genetic discovery with clinical and biological investigations, this study aims to improve understanding of the shared pathways between CRC and diabetes-related traits, identify biomarkers associated with disease progression, and provide a foundation for future precision medicine strategies in colorectal cancer.

Inclusion Criteria:

• Age 20 to 85 years
• Histologically confirmed colorectal cancer
• Newly diagnosed colorectal cancer at the time of enrollment
• No prior diagnosis of diabetes mellitus
• Ability to provide written informed consent

Exclusion Criteria:

• Age younger than 20 years or older than 85 years
• Pre-existing diagnosis of diabetes mellitus
• Severe obesity (body mass index ≥35 kg/m²)
• Pregnancy
• Inability or unwillingness to provide informed consent