Prospective analysis of circulating metabolites and breast cancer in EPIC

• Published in: BMC medicine Vol. 17; no. 1; pp. 178 - 13
• Main Authors: His, Mathilde, Viallon, Vivian, Dossus, Laure, Gicquiau, Audrey, Achaintre, David, Scalbert, Augustin, Ferrari, Pietro, Romieu, Isabelle, Onland-Moret, N. Charlotte, Weiderpass, Elisabete, Dahm, Christina C., Overvad, Kim, Olsen, Anja, Tjønneland, Anne, Fournier, Agnès, Rothwell, Joseph A., Severi, Gianluca, Kühn, Tilman, Fortner, Renée T., Boeing, Heiner, Trichopoulou, Antonia, Karakatsani, Anna, Martimianaki, Georgia, Masala, Giovanna, Sieri, Sabina, Tumino, Rosario, Vineis, Paolo, Panico, Salvatore, van Gils, Carla H., Nøst, Therese H., Sandanger, Torkjel M., Skeie, Guri, Quirós, J. Ramón, Agudo, Antonio, Sánchez, Maria-Jose, Amiano, Pilar, Huerta, José María, Ardanaz, Eva, Schmidt, Julie A., Travis, Ruth C., Riboli, Elio, Tsilidis, Konstantinos K., Christakoudi, Sofia, Gunter, Marc J., Rinaldi, Sabina
• Format: Journal Article
• Language: English
• Published: London BioMed Central 24.09.2019; BioMed Central Ltd; BMC
• Subjects: Adipose tissue; Adult; Aged; Amines; Amino acids; Arginine; Asparagine; Biogenic amines; Biological markers; Biomarkers; Biomarkers - analysis; Biomarkers - blood; Biomarkers - metabolism; Biomedicine; Breast cancer; Breast Neoplasms - blood; Breast Neoplasms - diagnosis; Breast Neoplasms - epidemiology; Cancer research; Care and treatment; Case-Control Studies; Cohort Studies; Community medicine, Social medicine: 801; Confidence intervals; Control methods; Development and progression; Diagnostic systems; Epidemiology; ErbB-2 protein; Estrogens; Etiology; Fasting; Female; Genetic aspects; Health risk assessment; Health risks; Health sciences: 800; Helsefag: 800; Hexose; Hormones; Humans; Incidence; Invasiveness; Life Sciences; Mass Spectrometry; Mass spectroscopy; Medical disciplines: 700; Medicine; Medicine & Public Health; Medisinske Fag: 700; Membrane lipids; Menopause; Metabolites; Metabolomics; Metabolomics - methods; Middle Aged; Monosaccharides; Novels; Phenols (Class of compounds); Phospholipids; Plant lipids; Progesterone; Prospective Studies; Prospective study; Regression analysis; Research Article; Risk; Risk Factors; Samfunnsmedisin, sosialmedisin: 801; Sex hormones; Skin cancer; Spectroscopy; Sphingolipids; Statistical analysis; VDP; Womens health; Greece; France; Norway; Germany; Metabolomics; Prospective study; Breast cancer
• ISSN: 1741-7015; 1741-7015
• DOI: 10.1186/s12916-019-1408-4

Background Metabolomics is a promising molecular tool to identify novel etiologic pathways leading to cancer. Using a targeted approach, we prospectively investigated the associations between metabolite concentrations in plasma and breast cancer risk. Methods A nested case-control study was established within the European Prospective Investigation into Cancer cohort, which included 1624 first primary incident invasive breast cancer cases (with known estrogen and progesterone receptor and HER2 status) and 1624 matched controls. Metabolites ( n  = 127, acylcarnitines, amino acids, biogenic amines, glycerophospholipids, hexose, sphingolipids) were measured by mass spectrometry in pre-diagnostic plasma samples and tested for associations with breast cancer incidence using multivariable conditional logistic regression. Results Among women not using hormones at baseline ( n  = 2248), and after control for multiple tests, concentrations of arginine (odds ratio [OR] per SD = 0.79, 95% confidence interval [CI] = 0.70–0.90), asparagine (OR = 0.83 (0.74–0.92)), and phosphatidylcholines (PCs) ae C36:3 (OR = 0.83 (0.76–0.90)), aa C36:3 (OR = 0.84 (0.77–0.93)), ae C34:2 (OR = 0.85 (0.78–0.94)), ae C36:2 (OR = 0.85 (0.78–0.88)), and ae C38:2 (OR = 0.84 (0.76–0.93)) were inversely associated with breast cancer risk, while the acylcarnitine C2 (OR = 1.23 (1.11–1.35)) was positively associated with disease risk. In the overall population, C2 (OR = 1.15 (1.06–1.24)) and PC ae C36:3 (OR = 0.88 (0.82–0.95)) were associated with risk of breast cancer, and these relationships did not differ by breast cancer subtype, age at diagnosis, fasting status, menopausal status, or adiposity. Conclusions These findings point to potentially novel pathways and biomarkers of breast cancer development. Results warrant replication in other epidemiological studies.