ArticleDiscover oncology2026
Impact of cytosine and piperine on colorectal cancer progression based on Mendelian randomization and functional validation.
Article in Discover oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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6 authors.
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Abstract
backgroundMetabolic dysregulation is increasingly implicated in tumorigenesis, but the metabolic profile of colorectal cancer (CRC) has not been fully elucidated. This study investigates the potential causal role of specific circulating metabolites in CRC development by integrating genetic instrumental variable analysis with biological validation in vitro.
methodsWe conducted a two-sample Mendelian randomization (MR) analysis using publicly available genome-wide association study (GWAS) datasets comprising 1,400 metabolites. Causal effects were estimated using the inverse variance weighted method and the weighted median approach. Heterogeneity and pleiotropy were evaluated to ensure robustness. Metabolites with consistent associations were subsequently investigated in CRC cell models to determine their functional effects.
resultsFifty-eight metabolites demonstrated potential causal links with CRC. Among them, cytosine was identified as a risk-enhancing metabolite (OR = 1.166, 95% CI = 1.020–1.333, P = 0.023), while piperine showed a protective effect (OR = 0.862, 95% CI = 0.768–0.967, P = 0.011). Functional experiments confirmed that cytosine promoted CRC cell proliferation, while piperine inhibited tumor growth.
conclusionThese findings suggest that specific circulating metabolites, such as cytosine and piperine, may influence colorectal cancer development through distinct biological mechanisms. Their involvement in metabolic pathways relevant to carcinogenesis merits further exploration, particularly regarding their potential translational applications.
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