Elodie Jobard

NMR Metabonomic Investigation of Early Biomarkers of Breast Cancer in the E3N Prospective Cohort
Elodie Jobard

Breast cancer is the most common cancer and the leading cause of cancer death in women worldwide. However, its incidence has slightly but steadily increased over the past three decades while its mortality rate has declined over the same period, thanks to advances in screening methods, early diagnosis and treatments. Breast cancer displays a high heterogeneity in terms of etiology and histology as well as prognosis, metastatic evolution and reponse to treatments. Thus, major challenges are breast cancer early detection, diagnosis and prevention. The purpose of this NMR metabonomic study is to prospectively investigate the aetiology of breast cancer in relation to the behaviour, diet and exposure profiles of the volunteers in the E3N study (Etude Epidémiologique auprès de femmes de la Mutuelle Générale de l’Education Nationale). The E3N study is a prospective cohort study that was initiated in 1990 to investigate factors associated with the most common types of cancer. It involves about 100,000 women living in France who were born between 1925 and 1950 and are covered by a national health insurance plan for teachers and coworkers. Participants completed self-questionnaires every 2 to 3 years on their lifestyle (diet, smoking habits, hormonal treatments, etc) and the evolution of their health. Biological data are also included in the E3N study with a collection of blood samples of 25, 000 volunteers before diagnosis and stored for subsequent biological analysis.
    Using a case-control design, 801 breast cancer cases with available plasma samples were identified and matched with an equal number of control subjects.  Each case has been matched at best with a control subject based on several parameters: age, centre of recruitment, date of sampling, fasting status and menopausal status. Plasma samples were analyzed by high-field 1H NMR (Nuclear Magnetic Resonance) spectroscopy at 600 MHz with the following objectives: (i) to identify early predictive biomarkers of breast cancer and (ii) to identify metabonomics profiles or biomarkers representative of lifestyle patterns. Indeed, because of its large size this study has great power to identify early biomarkers of breast cancer but also to better understand its aetiology. We present here the first results of the NMR metabonomic analysis of the E3N study and in particular the identification of the main sources of systematic variations. Further analysis of the data is currently in progress.