Can serum metabolic signatures inform on the relationship between healthy lifestyle and colon cancer risk?

TL;DR

This study explores how a healthy lifestyle reduces colon cancer risk and whether blood metabolites can explain this relationship, finding stronger effects in men and no link after adjusting for lifestyle.

Contribution

The study identifies serum metabolic signatures linked to a healthy lifestyle but finds they do not independently predict colon cancer risk after accounting for lifestyle factors.

Findings

A healthy lifestyle was inversely associated with colon cancer risk (OR 0.79 per SD increase).

The metabolic signature of the healthy lifestyle was moderately correlated with lifestyle factors (r = 0.59).

After adjusting for lifestyle factors, the metabolic signature showed no association with colon cancer risk.

Abstract

Colon cancer is strongly influenced by lifestyle factors. Sociodemographic factors like sex and socioeconomic position (SEP) might modulate the relationship between lifestyle and colon cancer risk. Metabolomics offers potential to uncover biological mechanisms linking lifestyle and colon cancer.

Lifestyle and untargeted metabolomic data were available from a nested case–control study within the European Prospective Investigation into Cancer and Nutrition (EPIC), including 1,067 colon cancer cases and 1,067 controls matched on age, sex, study centre, and blood collection time. Serum samples were analyzed using liquid chromatography-mass spectrometry. The Healthy Lifestyle Index (HLI) score was derived from smoking habits, alcohol intake, body mass index (BMI), physical activity, and diet. Penalised regression was applied in controls to derive metabolic signatures for the HLI and the lifestyle components. Associations of lifestyle factors and the metabolic signatures with colon cancer risk were estimated in conditional logistic regression models, overall and by sex and SEP.

The HLI score was inversely associated with colon cancer risk, with an odds ratio (OR) per 1-standard deviation (SD) increment equal to 0.79; 95% CI: 0.71, 0.87. The metabolic signature of HLI, comprising 130 features, was moderately correlated with HLI (r = 0.59; 94% CI: 0.56, 0.61), and was inversely associated with colon cancer risk (OR = 0.86; 95% CI: 0.78, 0.95). After adjustment for the HLI score, the association of the metabolic signature of HLI and colon cancer risk was null (OR = 1.00, 95% CI 0.88, 1.13). Associations of lifestyle factors and the metabolic signature with colon cancer risk were consistently stronger for men than for women and did not differ by SEP.

In this study across seven European countries, healthy lifestyle was inversely associated with colon cancer risk, with stronger associations in men than women and no differences across SEP. However, the serum metabolic signatures after adjustment for lifestyle factors were not found to be associated with colon cancer risk, suggesting that lifestyle impacts colon cancer through mechanisms not captured by the signatures.

The online version contains supplementary material available at 10.1186/s40170-025-00388-0.

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