biostudies-literatureSmith-Byrne KCancer Research UKWorld Health OrganizationNational Institute for Health Research (NIHR)NCI NIH HHSNational Institutes of HealthWellcome Trust1966-1974https://www.ebi.ac.uk/biostudies/studies/S-EPMC9530646biostudies-literatureUnknown31(10)<h4>Background</h4>Tobacco exposure causes 8 of 10 lung cancers, and identifying additional risk factors is challenging due to confounding introduced by smoking in traditional observational studies.<h4>Materials and methods</h4>We used Mendelian randomization (MR) to screen 207 metabolites for their role in lung cancer predisposition using independent genome-wide association studies (GWAS) of blood metabolite levels (n = 7,824) and lung cancer risk (n = 29,266 cases/56,450 controls). A nested case-control study (656 cases and 1,296 matched controls) was subsequently performed using prediagnostic blood samples to validate MR association with lung cancer incidence data from population-based cohorts (EPIC and NSHDS).<h4>Results</h4>An MR-based scan of 207 circulating metabolites for lung cancCancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive OncologyCirculating Isovalerylcarnitine and Lung Cancer Risk: Evidence from Mendelian Randomization and Prediagnostic Blood Measurements.PMC953064600129017U19CA203654C18281/A2901929019U19 CA203654Agudo ASandanger TMKaaks RGuida FNost THAmos CIRichards JBSchulze MBWeiderpass EImaz LHung RJGrankvist KKuhn TCerani AGram ITMcKay JDSchibli DBrennan PZhou SBarranco MRVineis PChirlaque-Lopez MDPala VAleksandrova KBarricarte ASmith-Byrne KJohansson MMartin RMHan JTravis RCBochers CHRobbins HAfalseCirculating Isovalerylcarnitine and Lung Cancer Risk: Evidence from Mendelian Randomization and Prediagnostic Blood Measurements.<h4>Background</h4>Tobacco exposure causes 8 of 10 lung cancers, and identifying additional risk factors is challenging due to confounding introduced by smoking in traditional observational studies.<h4>Materials and methods</h4>We used Mendelian randomization (MR) to screen 207 metabolites for their role in lung cancer predisposition using independent genome-wide association studies (GWAS) of blood metabolite levels (n = 7,824) and lung cancer risk (n = 29,266 cases/56,450 controls). A nested case-control study (656 cases and 1,296 matched controls) was subsequently performed using prediagnostic blood samples to validate MR association with lung cancer incidence data from population-based cohorts (EPIC and NSHDS).<h4>Results</h4>An MR-based scan of 207 circulating metabolites for lung canc2022-01-01T00:00:00Z2022 Oct2026-05-10T03:19:58.92Z2025-04-06T03:41:54.545ZS-EPMC95306463583946110.1158/1055-9965.EPI-21-1033