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

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.

Eligibility Criteria:
Inclusion Criteria:

1. Subjects free of malignancy

   * men or women 40-70 yrs aged
2. 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:

1. 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
2. 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)