Associations between circulating metabolites and incidence of breast, prostate, lung and colorectal cancers in the HUNT Study and UK Biobank

Abstract Background Breast, prostate, lung and colorectal cancers are the most common cancers in both women and men globally. The role of circulating metabolites, including lipoprotein subfractions, in the development of these cancers remains unclear. This prospective cohort study aimed to explore the associations between circulating metabolites and the incidence of these cancers. Methods From two large population-based cohorts, the Trøndelag Health Study (HUNT) and the UK Biobank (UKBB), 132 lipoprotein subfractions and metabolites, quantified using nuclear magnetic resonance spectroscopy, were available for participants ( n = 16,877 in HUNT3, n = 480,840 in UKBB). Cox regression was used to investigate the associations with incident cancers. Results During a mean follow-up time of 14 years, 549 women and 741 men in HUNT3 and 12,112 women and 14,749 men in UKBB developed breast, prostate, lung or colorectal cancer. In the UKBB, higher levels of several subfractions of lipoproteins including VLDL and LDL were associated with a decreased incidence of prostate and lung cancers (cholesterol in large LDL: HR per 1-SD increment 0.84, 95% CI 0.81–0.87 for lung cancer). Similar associations were observed between albumin, some fatty acids, and lung cancer. However, no clear associations were observed in HUNT3. Conclusion Several lipoprotein subfractions and circulating metabolites were associated with a reduced incidence of lung cancer, predominantly in UKBB. Although no specific lipid or metabolite profile was associated with the most common cancers, the observed associations showed the same direction of effect across cohorts, despite not reaching statistical significance in HUNT3. Our results highlight promising directions for future research into metabolic biomarkers and their potential role in cancer prevention.