The Effect of Colon Cancer on Muscle Gene Expression, Body Composition, Muscle Function, and Muscle Metabolism

Study Overview
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Brief Summary
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Rationale: Cancer cachexia is a complex metabolic syndrome characterized by clinically relevant loss of muscle mass with or without loss of fat mass. To determine how treatment methods can be most effective, full insight in changes in gene expression, body composition, muscle function and muscle metabolism are of great importance. Objective: Main aim of the study is to investigate the differences in gene expression, body composition, muscle function and muscle metabolism in colon cancer patients compared to controls. Study design: Observational study Study population: 40 colon cancer patients undergoing a tumor resection (30 primary tumor and 10 liver metastases) and 15 control patients undergoing an inguinal hernia repair (♂, 10) or an abdominal hysterectomy (♀, 5). Main study parameters/endpoints: Primary study parameter will be gene expression (transcriptomic and polymerase chain reaction analyses of muscle biopsies). Secondary parameters will be body composition (determined in available CT scans and bio impedance analysis and with DEXA), muscle function parameters (grip and knee flexion/extension strength and measured in a biopsy), metabolic markers (measured in fat and muscle biopsies), biochemical markers (measured in blood/serum) and gene expression of fat biopsies. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The investigators expect no additional risk for the subjects due to the proposed measurements. Biopsies will be taken during the planned operation and therefore is not expected to cause a significant increase in burden for the patient. All other measurements are non-invasive, observational measurements with no risk of any harmful side effects.

Official Title
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The Effect of Colon Cancer on Muscle Gene Expression, Body Composition, Muscle Function, and Muscle Metabolism

Conditions
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Cachexia; Cancer

Intervention / Treatment
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* Other: Not applicable, observational study


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: CC patients: In order to be eligible to participate in this study, a subject must meet all of the following inclusion criteria: Diagnosed with primary colon cancer (30) or liver metastases due to colon cancer(10) Eligible for a primary tumor or liver metastases resection procedure Controls: Eligible for an inguinal hernia repair (♂, 10) or an abdominal hysterectomy (♀, 5) Exclusion Criteria: CC patients: A potential subject who meets any of the following criteria will be excluded from participation in this study: Having had chemotherapy or an operational procedure of the abdomen in the past 6 months Suffering from malabsorption Controls: Having had treatment for previous or current tumors
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Primary colon cancer<br> | Other: Not applicable, observational study<br>* Not applicable, observational study<br>|
| Liver metastases<br> | Other: Not applicable, observational study<br>* Not applicable, observational study<br>|
| Inguinal hernia (control)<br> | Other: Not applicable, observational study<br>* Not applicable, observational study<br>|
| Abdominal hysterectomy (control)<br> | Other: Not applicable, observational study<br>* Not applicable, observational study<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Muscle gene expression | Muscle gene expression measured by microarray in a muscle biopsy taken from the rectus abdominis | Biopsy during surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body composition | Measured using single slice staining of CT scan made for diagnostic purposes. | Before surgery | 
| Muscle function | Measured using hand-grip strength | Before surgery | 
| Muscle protein metabolism | Measured in a muscle biopsy taken from the rectus abdominis | Biopsy during surgery | 
| Adipose tissue gene expression | Adipose tissue gene expression measured using PCR or micro-array in abdominal and subcutaneous fat | Biopsy during surgery | 
| Cytokine parameters in the blood | Blood plasma cytokine levels measured using multiplex or similar technique | Blood taken prior to surgery | 
| Micro-nutrient parameters in the blood | Micro-nutrient levels in the blood measured using LCMS, ELISA or similar techniques | Blood taken prior to surgery | 
| Cholesterol levels in the blood | Cholesterol levels in the blood measured by GCMS | Blood taken prior to surgery |