Prospective analysis of circulating metabolites and breast cancer in EPIC
Posted on 2019-09-24 - 03:37
Abstract 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.
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His, Mathilde; Viallon, Vivian; Dossus, Laure; Gicquiau, Audrey; Achaintre, David; Scalbert, Augustin; et al. (2019). Prospective analysis of circulating metabolites and breast cancer in EPIC. figshare. Collection. https://doi.org/10.6084/m9.figshare.c.4675355.v1
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AUTHORS (45)
MH
Mathilde His
VV
Vivian Viallon
LD
Laure Dossus
AG
Audrey Gicquiau
DA
David Achaintre
AS
Augustin Scalbert
PF
Pietro Ferrari
IR
Isabelle Romieu
NO
N. Onland-Moret
EW
Elisabete Weiderpass
CD
Christina Dahm
KO
Kim Overvad
AO
Anja Olsen
AT
Anne Tjønneland
AF
Agnès Fournier
JR
Joseph Rothwell
GS
Gianluca Severi
TK
Tilman Kühn
RF
Renée Fortner
HB
Heiner Boeing