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Do blood metabolites flag future breast cancer in EPIC?

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In 1624 EPIC breast-cancer cases matched to 1624 controls, higher arginine, asparagine, and several phosphatidylcholines tracked lower risk, while acylcarnitine C2 tracked higher risk.

Source

Prospective analysis of circulating metabolites and breast cancer in EPIC

His M, Viallon V, Dossus L, et al. · BMC medicine · 2019

doi.org/10.1186/s12916-019-1408-4Read the full paper ↗105 citationscc by

Study at a glance

Design
Case-control — Nested case-control in EPIC: 1624 incident invasive breast cancers matched 1:1 to controls; 127 targeted plasma metabolites by mass spectrometry.
N
N=3248 · 1624 cases and 1624 matched controls (after excluding pregnancies from 1626/1626 eligible).
Population
Women in the European Prospective Investigation into Cancer with pre-diagnostic plasma and known ER/PR/HER2 status.
Outcome
Incident invasive breast cancer (overall and by subtype) per SD metabolite concentration, especially among non-users of hormones.

Structured fields used in claim comparison tables when every cited study has a complete layer.

What they did

Nested 1624 incident invasive breast cancers (known ER/PR/HER2) 1:1 to controls, measured 127 metabolites in pre-diagnostic plasma by mass spectrometry, and used multivariable conditional logistic regression with multiple-testing control.

What they found

Among 2248 women not using hormones at baseline, arginine (OR per SD 0.79), asparagine (0.83), and several PCs (about 0.83–0.85) were inversely associated, while C2 was positively associated (OR 1.23). In the full cohort only C2 (OR 1.15) and PC ae C36:3 (OR 0.88) remained, without clear heterogeneity by subtype, menopause, fasting, or adiposity.

The limits

What it doesn't show

A single baseline blood draw and observational matching cannot prove metabolites cause breast cancer; findings need replication.

Key terms

EPIC
European Prospective Investigation into Cancer cohort that nested this case-control.
Nested case-control
Cases and matched controls sampled from a prospective cohort using pre-diagnostic samples.
Acylcarnitine C2
Acetylcarnitine involved in mitochondrial fatty-acid transport; higher levels tracked higher breast-cancer risk.
Phosphatidylcholines (PCs)
Glycerophospholipids; several species were inversely associated with risk in non-users of hormones.
Conditional logistic regression
Matched-pair model used for odds ratios per SD metabolite.
Multiple-testing control
Bonferroni (P<0.05/127) and FDR α=0.05 applied to 127 metabolites.

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Design was a:

Common questions

How many cases and controls?

1624 incident invasive breast cancers and 1624 matched controls.

How many metabolites?

127 (acylcarnitines, amino acids, biogenic amines, glycerophospholipids, hexose, sphingolipids).

What was inversely associated in non-users of hormones?

Arginine, asparagine, and several phosphatidylcholines.

What was positively associated?

Acylcarnitine C2 (OR 1.23 in non-users; 1.15 overall).

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