Glucose Homeostasis and Shared Genetic Factors in Colorectal Cancer (BRIDGE-CRCDM)
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.
Tutkimuksen yleiskatsaus
Tila
Yksityiskohtainen kuvaus
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.
Opintotyyppi
Ilmoittautuminen (Arvioitu)
Yhteystiedot ja paikat
Opiskeluyhteys
- Nimi: Yih Jong Chern, MD
- Puhelinnumero: +886-3-3281200 - 2101
- Sähköposti: ufo789.ufo789@gmail.com
Osallistumiskriteerit
Kelpoisuusvaatimukset
Opintokelpoiset iät
- Aikuinen
- Vanhempi Aikuinen
Hyväksyy terveitä vapaaehtoisia
Näytteenottomenetelmä
Tutkimusväestö
Kuvaus
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
Opintosuunnitelma
Miten tutkimus on suunniteltu?
Suunnittelun yksityiskohdat
Kohortit ja interventiot
Ryhmä/Kohortti |
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Colorectal Cancer Cohort
Patients with newly diagnosed colorectal cancer without pre-existing diabetes mellitus at enrollment.
Participants will be prospectively followed for 48 weeks to evaluate the development of diabetes mellitus and changes in glucose homeostasis.
Serial assessments will include fasting glucose, HbA1c, insulin, C-peptide, inflammatory biomarkers, immune cell profiles, and genetic analyses.
Blood samples and available colorectal tissue specimens will be collected for the evaluation of shared genetic variants, SMAD7-related pathways, and molecular mechanisms linking glucose dysregulation and colorectal cancer.
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Mitä tutkimuksessa mitataan?
Ensisijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
|---|---|---|
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Association between shared genetic variants and glucose homeostasis biomarkers
Aikaikkuna: Baseline to Week 48
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Concentrations of fasting plasma glucose (mg/dL), hemoglobin A1c (%), fasting insulin (μIU/mL), and C-peptide (ng/mL) will be measured at baseline and during follow-up.
Associations between identified shared genetic variants (e.g., SMAD7) and glucose homeostasis biomarkers will be assessed using regression analyses.
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Baseline to Week 48
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Incidence of colorectal cancer-related outcomes
Aikaikkuna: Baseline to Week 48
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Occurrence of colorectal cancer-related outcomes, including recurrence, progression, or mortality, during the follow-up period.
Event rates (%) and time-to-event outcomes will be recorded and analyzed according to genetic variant status.
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Baseline to Week 48
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Toissijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
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Expression level of SMAD7 in systemic blood and colorectal tissue
Aikaikkuna: Baseline to Week 48
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SMAD7 expression levels will be measured in systemic blood and local colorectal tissue samples using quantitative polymerase chain reaction (qPCR) or RNA sequencing.
Expression levels will be reported as relative expression values, normalized gene expression counts, or fold change across predefined exposure groups.
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Baseline to Week 48
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Concentrations of inflammatory and immunological biomarkers in systemic blood and colorectal tissue
Aikaikkuna: Baseline to Week 48
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Inflammatory and immunological biomarkers will be measured in systemic blood and local colorectal tissue samples using enzyme-linked immunosorbent assay, multiplex cytokine assay, immunohistochemistry, flow cytometry, or transcriptomic profiling, as applicable.
Outcomes will include biomarker concentrations, staining scores, immune cell proportions, or normalized expression values across predefined exposure groups.
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Baseline to Week 48
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Proportions of T cell subpopulations in systemic blood and colorectal tissue
Aikaikkuna: Baseline to Week 48
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T cell subpopulations, including cytotoxic T cells, regulatory T cells, helper T cells, and other relevant T cell subsets, will be measured in systemic blood and local colorectal tissue samples using flow cytometry, immunohistochemistry, or single-cell RNA sequencing, as applicable.
Outcomes will be reported as percentages of total lymphocytes, percentages of CD3+ T cells, cell counts, staining scores, or normalized cell abundance estimates.
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Baseline to Week 48
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Yhteistyökumppanit ja tutkijat
Sponsori
Opintojen ennätyspäivät
Opi tärkeimmät päivämäärät
Opiskelun aloitus (Arvioitu)
Ensisijainen valmistuminen (Arvioitu)
Opintojen valmistuminen (Arvioitu)
Opintoihin ilmoittautumispäivät
Ensimmäinen lähetetty
Ensimmäinen toimitettu, joka täytti QC-kriteerit
Ensimmäinen Lähetetty (Todellinen)
Tutkimustietojen päivitykset
Viimeisin päivitys julkaistu (Todellinen)
Viimeisin lähetetty päivitys, joka täytti QC-kriteerit
Viimeksi vahvistettu
Lisää tietoa
Tähän tutkimukseen liittyvät termit
Avainsanat
Muita asiaankuuluvia MeSH-ehtoja
- Endokriinisen järjestelmän sairaudet
- Neoplasmat sivustoittain
- Neoplasmat
- Metaboliset sairaudet
- Suoliston sairaudet
- Ruoansulatuskanavan kasvaimet
- Ruoansulatuskanavan kasvaimet
- Ruoansulatuskanavan sairaudet
- Ruoansulatuskanavan sairaudet
- Suoliston kasvaimet
- Peräsuolen sairaudet
- Glukoosiaineenvaihduntahäiriöt
- Paksusuolen sairaudet
- Ravitsemukselliset ja aineenvaihduntataudit
- Kolorektaaliset kasvaimet
- Diabetes mellitus
- Hyperglykemia
Muut tutkimustunnusnumerot
- ChangGungMH202600418A3
- 202600418A3 (Muu tunniste: Chang Gung Medical Foundation Institutional Review Board)
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