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

BackgroundBreast, 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. ObjectiveThis prospective cohort study, including two large population-based cohorts, aimed to explore the associations between circulating metabolites and the incidence of breast, prostate, lung and colorectal cancers. MethodsFrom the Trondelag 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=260,805 in UKBB). Cox regression was used to investigate the associations with incident cancers. ResultsDuring a mean follow-up time of 14 years, 549 women and 741 men developed breast (n= 283), prostate (n=452), lung (n=175) or colorectal (n=380) cancer in HUNT3, while 6679 women and 8248 men developed breast (n=4516), prostate (n=5576), lung (n=1985) or colorectal (n=2850) cancer in UKBB. In the UKBB, higher levels of several subfractions of lipoproteins including VLDL and LDL were associated with a slight decreased incidence of prostate and lung cancers (cholesterol in large LDL: HR per 1-SD increment 0.90, 95% CI 0.86-0.94 for lung cancer). Similar associations were observed between albumin, some fatty acids, and lung cancer. However, no clear associations were observed in HUNT3. ConclusionSeveral lipoprotein subfractions and circulating metabolites were associated with a reduced incidence of lung cancer, predominantly in UKBB. Although no conclusive evidence was found for a specific lipid or metabolite profile associated with the incidence of the most common cancers, the observed associations were generally consistent across cohorts. Our results highlight promising directions for future research into metabolic biomarkers and their potential role in cancer prevention.