Prospective analysis of circulating metabolites and breast cancer in EPIC
AuthorHis, 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 Turzanski; Boeing, Heiner; Trichopoulou, Antonia; Karakatsani, Anna; Martimianaki, Georgia; Masala, Giovanna; Sieri, Sabina; Tumino, Rosario; Vineis, Paolo; Panico, Salvatore; van Gils, Carla H.; Nøst, Therese Haugdahl; Sandanger, Torkjel M; Skeie, Guri; Quirós, José Ramón; Agudo, Antonio; Sánchez, María-José; Amiano, Pilar; Huerta, José María; Ardanaz, Eva; Schmidt, Julie A.; Travis, Ruth C.; Riboli, Elio; Tsilidis, Konstantinos K.; Christakoudi, Sofia; Gunter, Mark J.; Rinaldi, Sabina
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.