Evidence map›Paper›PMID 42104324›Full record

ArticleBMC cancer2026

Smoking metabolic signature modifies the risk of colorectal cancer and interacts with genetic susceptibility: a large-scale prospective cohort study.

Jing Wang, Jiawei Zhang, Zhuoyi Wu, Yuqiang Zhao, Shiyin Meng, Wenjie Xuan, Jing Ni

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Article in BMC cancer, 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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1 · What the graph read from it

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

7 authors.

Jing Wang *Department of Epidemiology and Biostatistics, Center for Big Data and Population Health of IHM, School of Public Health, Anhui Medical University, Hefei, China.
Jiawei Zhang *Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
Zhuoyi WuDepartment of Epidemiology and Biostatistics, Center for Big Data and Population Health of IHM, School of Public Health, Anhui Medical University, Hefei, China.
Yuqiang ZhaoDepartment of Epidemiology and Biostatistics, Center for Big Data and Population Health of IHM, School of Public Health, Anhui Medical University, Hefei, China.
Shiyin MengDepartment of Epidemiology and Biostatistics, Center for Big Data and Population Health of IHM, School of Public Health, Anhui Medical University, Hefei, China.
Wenjie XuanDepartment of Epidemiology and Biostatistics, Center for Big Data and Population Health of IHM, School of Public Health, Anhui Medical University, Hefei, China.
Jing NiDepartment of Epidemiology and Biostatistics, Center for Big Data and Population Health of IHM, School of Public Health, Anhui Medical University, Hefei, China. nijing@ahmu.edu.cn.

Funding

Center for Big Data and Population Health of IHM JKS2023008National Natural Science Foundation of China 82103932Natural Science Foundation in Higher Education of Anhui 2024AH050692Research Fund of Anhui Institute of translational medicine 2023zhyx-C07
6 · The paper itself

Abstract

backgroundSmoking tobacco is proven to be associated with higher colorectal cancer (CRC) risk. However, the metabolic pathways of smoking and how they relate to CRC risk are unclear.

methodsA total of 227,898 participants from the UK Biobank were included. A two-stage strategy with a combination of linear regression and Mendelian randomization analysis was employed to identify smoking-related metabolites. Then the elastic net (EN) regression model was used to construct smoking-related metabolic signature. Multivariable Cox regression, Mediation analysis, and interaction analysis were employed to illustrate the associations of smoking and smoking related metabolic signature on the risk of CRC. Furthermore, the interaction between genetic susceptibility and smoking metabolic signature was estimated based on relative excess risk due to interaction (RERI) and multiplicative-scale interaction.

resultsDuring a follow-up of 12.5 years, 3,328 incident CRC patients were observed. We identified 71 smoking-related metabolites and screened 42 of them metabolites by EN model to construct smoking-related metabolic signature. We observed smoking and smoking metabolic signature were both associated with the elevated risk of CRC, with a hazard ratio (HR) value of 1.27 and 1.38, respectively. Mediation analysis revealed metabolic signature can mediate 10.03% in the association between smoking and CRC risk. The additive interaction between genetic susceptibility and metabolic signature was statistically significant (RERI = 0.70, 95% confidence interval [CI] = 0.29-1.10).

conclusionThe detrimental impact of smoking on CRC risk is mediated partially by smoking metabolic signature, which is synergistic with genetic susceptibility.

Indexed as

Colorectal NeoplasmsGenetic Predisposition to DiseaseMetabolomeSmokingAgedFemaleHumansMaleMendelian Randomization AnalysisMiddle AgedPolymorphism, Single NucleotideProspective StudiesRisk FactorsUK BiobankUnited KingdomCigarette smokeColorectal cancerGenetic susceptibilityInteraction analysisMetabolic signature

Identifiers

PMID42104324
PMCPMC13326479

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.