Impact of Exercise and Hyperlipidic Meal on Free Circulating DNA in Patients With Metastatic Colonic Cancer and Healthy Subjects (ASRHACOLS)

Impact of Exercise and Hyperlipidic Meal on Free Circulating DNA in Patients With Metastatic Colonic Cancer and Healthy Subjects

Impact of Sport Practice and Hyperlipidic Meal on Free Circulating DNA in Patients With Metastatic Colonic Cancer and Healthy Subjects. Physiological Pilot Study

The study of circulating tumoral DNA makes it possible to study, without invasive procedures or pathological studies, the tumoral DNA circulating in the blood of a patient and its various alterations. In patients with colon-rectal cancer with resected tumor, circulating tumor DNA can be used as a predictive biomarker of metastatic relapse of cancer. However, the routine extension of circulating tumoral DNA remains limited due to several difficulties. One of the pifalls that circulating tumor DNA is greatly diluted by healthy circulating DNA from non-tumor cells. The amount of healthy circulating DNA has been described as being influenced by certain physiological parameters. The aim of the study is to increase knowledge on the influence of physiological factors associated with sports activity and meal on the release kinetics of circulating DNA.

20 subjects free of malignancy (Male-Female Ratio 2 to 1) the variation in the concentration of DNA circulating between the value measured on an empty stomach after 1 hour of rest, then at the end of each of the successive stages of moderate intensity physical effort: pedaling 15 minutes at 75 Watt then 100 Watt of the ergometer. Dosages will be repeated after 15, 30 and 60 minutes of recovery. After an hour of recovery, the subject will be asked to consume a meal rich in fat. The circulating DNA will be measured 2 hours after the end of the meal. 40 patients with colon cancer will be enrolled for a two visit study. The first visit will be planned at the first cycle of chemotherapy, before the chemotherapy. At this visit, the influence of exercise on plasma concentrations of circulating free DNA will also be studied in 40 patients with colon cancer. Free circulating DNA will be measured on an empty stomach after 1 hour of rest, then immediately after low-intensity physical effort : pedaling 3 minutes at the 30 Watt level of the ergometer) and after 15, 30 and 60 minutes of recovery. After an hour of recovery, the subject will be proposed to consume a meal rich in fat. The circulating DNA will be measured 2 hours after the end of the meal. The second visit will be planned at the first second of chemotherapy, before the chemotherapy. Free circulating DNA will be measured on an empty stomach after 1 hour of rest, then immediately after low-intensity physical effort : pedaling 3 min at the 30 Watt level of the ergometer, and after 15, 30 and 60 minutes of recovery.

Low intensity physical effort and meal (visit 1, day of cycle 1 chemotherapy) and low intensity physical effort (visit 2, day of cycle 2 chemotherapy)

Multiple measure of circulating DNA: on an empty stomach, at the end of the physical effort, after 15, 30 and 60 minutes of rest, 120 minutes after an hyperlipidic meal. An additional measure will occur for subjects free of malignancy during the effort.

Variation in the concentration of circulating DNA between the value measured after 1 hour of rest, during and at recovery of moderate intensity physical effort

Variation in the concentration of circulating DNA between the value measured before and after an hyperlipidic meal in subjects free of malignancy

Variation in the concentration of circulating DNA between the value measured after 1 hour of rest, during and at recovery of low intensity physical effort

Variation in the concentration of circulating DNA between the value measured before and after an hyperlipidic meal

Inclusion Criteria: Subjects free of malignancy men or women 40-70 yrs aged Patients with colon cancer men or women 18-85 yrs aged Biopsy-proven colon cancer with indication to chemiotherapy Chemiotherapy (first line or second line) not started Exclusion Criteria: All subjects Ischemic cardiac history known heart disease blood hemoglobin concentration <8g / dl Acute or chronic systemic illnesses, (apart from diabetes, essential or secondary hypertension for patients) Pregnancy or breastfeeding or in progress Subjects free of malignancy Cardiovascular risk factor (active smoking or greater than 10 pack-years, diabetes, hypertension or known dyslipidemia not controlled by the diet) Glomerular filtration rate estimated by the CKD epi (Chronic Kidney Disease - Epidemiology Collaboration) formula < 60 ml.min-1.1.73 m-² Contraindication to exercise Drug taking in progress (except estrogen-progestogen contraception)

Individual participant data (IPD) that underlie results in publication could be shared. IPD detailed in the protocol of a planned metaanalysis could be shared

Individual participant data (IPD) that underlie results in publication could be shared. IPD detailed in the protocol of a planned metaanalysis could be shared Supporting Information: Study Protocol Informed Consent Form (ICF) Time Frame: Two years after the last publication Access Criteria: Data sharing must be accepted by the sponsor and the PI based on a scientific project and scientific involvement of the PI team. Collaboration will be fostered. Data sharing must respect the agreements made with funders. Teams wishing obtain IPD must meet the sponsor and IP team to present scientific (and commercial) purpose, IPD needed, format of data transmission, and timeframe. Technical feasibility and financial support will be discussed before mandatory contractual agreement. Processing of shared data must comply with European General Data Protection Regulation (GDPR).