His, MathildeViallon, VivianDossus, LaureGicquiau, AudreyAchaintre, DavidScalbert, AugustinFerrari, PietroRomieu, IsabelleOnland-Moret, N. CharlotteWeiderpass, ElisabeteDahm, Christina C.Overvad, KimOlsen, AnjaTjønneland, AnneFournier, AgnèsRothwell, Joseph A.Severi, GianlucaKühn, TilmanFortner, Renée T.Boeing, HeinerTrichopoulou, AntoniaKarakatsani, AnnaMartimianaki, GeorgiaMasala, GiovannaSieri, SabinaTumino, RosarioVineis, PaoloPanico, Salvatorevan Gils, Carla H.Nøst, Therese H.Sandanger, Torkjel M.Skeie, GuriQuirós, J. RamónAgudo, AntonioSanchez-Perez, Maria-JoseAmiano, PilarHuerta, José MaríaArdanaz, EvaSchmidt, Julie A.Travis, Ruth C.Riboli, ElioTsilidis, Konstantinos K.Christakoudi, SofiaGunter, Marc J.Rinaldi, Sabina2020-08-252020-08-252019-09-24His M, Viallon V, Dossus L, Gicquiau A, Achaintre D, Scalbert A, et al. Prospective analysis of circulating metabolites and breast cancer in EPIC. BMC Med. 2019 Sep 24;17(1):178.http://hdl.handle.net/10668/3173Background: 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.enBreast cancerMetabolomicsProspective studyBreast neoplasmsNeoplasias de la mamaMetabolómicaEstudios prospectivosAdultMedical Subject Headings::Persons::Persons::Age Groups::Adult::AgedMedical Subject Headings::Chemicals and Drugs::Biological Factors::Biological Markers::Biomarkers, PharmacologicalMedical Subject Headings::Diseases::Neoplasms::Neoplasms by Site::Breast NeoplasmsMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control StudiesMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort StudiesMedical Subject Headings::Check Tags::FemaleMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Information Science::Information Science::Data Collection::Vital Statistics::Morbidity::IncidenceMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Chemistry Techniques, Analytical::Mass SpectrometryMedical Subject Headings::Disciplines and Occupations::Natural Science Disciplines::Biological Science Disciplines::Biochemistry::MetabolomicsMedical Subject Headings::Persons::Persons::Age Groups::Adult::Middle AgedMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Prospective StudiesMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk FactorsMedical Subject Headings::Persons::Persons::Age Groups::Adultresearch article31547832Acceso abierto10.1186/s12916-019-1408-41741-7015PMC6757362