Effects of Endocrine Disruptors on the Gut Microbiota and Assessment of Their Impact on Colorectal Cancer Development (PERMICA)

Overview

Colorectal cancer is the third most common cancer worldwide, yet it was the second leading cause of cancer-related deaths in 2020. The average French population faces a colorectal cancer risk partly linked to lifestyle factors. The majority of colorectal cancer cases (approximately 85%) are not caused by hereditary mutations. Environmental factors, such as lifestyle or diet (notably through endocrine disruptors), can affect the gut microbiota (a collection of microorganisms - bacteria, viruses, parasites, and fungi - residing in the intestinal environment) and lead to disturbances in its composition, referred to as dysbiosis. While the mechanisms underlying dysbiosis associated with colorectal cancer remain poorly understood, the involvement of certain ingested substances, known as xenobiotics, is increasingly suspected, including endocrine disruptors. Among the most common endocrine disruptors found in water and food are parabens and phthalates, which will be examined in detail in this study. These substances may be directly involved in the development of colorectal cancer and in response to its treatment. The main objective of this studie is to characterize the relationship between colorectal cancer diagnosis, activity/composition of the gut microbiota, and patients' exposure to selected endocrine disruptors, particularly parabens and phthalates.

Methodology: Pilot, single-center regional study, with a descriptive and comparative design (patients with colorectal cancer / patients without suspected colorectal cancer = controls). In each group, a stool, hair and urine sample will be collected and an endocrine disruptor exposure questionnaire completed. Sample Size and Duration: A total of 200 patients will be included, divided into two groups of 100 patients (100 patients with colorectal cancer and 100 patients without suspected colorectal cancer). The inclusion period will last 48 months, with each participant enrolled for a maximum of one month. Routine care data will be collected over 5 years. The total duration of the clinical investigation will be approximately 9 years. Expected Outcomes: The investigators aim at determining whether the most common endocrine disruptors in the French population are involved in colorectal carcinogenesis and if these substances are correlated with dysbiotic colorectal microbiota. The findings from this study should help identify the endocrine disruptors most frequently associated with colorectal cancer and thereby enhance vigilance regarding these substances. Benefits for Patients: There are no individual but collective benefits, as the results will colorectal cancer related knowledge and its relationship with lifestyle.