Journal Article

DKFZ-2022-01496

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Circulating Isovalerylcarnitine and Lung Cancer Risk: Evidence from Mendelian Randomization and Pre-Diagnostic Blood Measurements.

Smith-Byrne, K. ; Cerani, A. ; Guida, F. ; Zhou, S. ; Agudo, A. ; Aleksandrova, K. ; Barricarte, A. ; Rodríguez-Barranco, M. ; Borchers, C. H. ; Gram, I. T. ; Han, J. ; Amos, C. I. ; Hung, R. J. ; Grankvist, K. ; Nøst, T. H. ; Imaz, L. ; Chirlaque-López, M. D. ; Johansson, M. ; Kaaks, R.DKFZ* ; Kühn, T.DKFZ* ; Martin, R. M. ; McKay, J. D. ; Pala, V. ; Robbins, H. A. ; Sandanger, T. M. ; Schibli, D. ; Schulze, M. B. ; Travis, R. C. ; Vineis, P. ; Weiderpass, E. ; Brennan, P. ; Johansson, M. ; Richards, J. B.

2022
AACR Philadelphia, Pa.

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Please use a persistent id in citations: doi:10.1158/1055-9965.EPI-21-1033

Abstract: 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.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 1,309 matched controls) was subsequently performed using pre-diagnostic blood samples to validate MR association with lung cancer incidence data from population-based cohorts (EPIC and NSHDS).An MR-based scan of 207 circulating metabolites for lung cancer risk identified that blood isovalerylcarnitine (IVC) was associated with a decreased odds of lung cancer after accounting for multiple testing (Log10-OR = 0.43, 95% CI: 0.29-0.63). Molar measurement of IVC in pre-diagnostic blood found similar results (Log10-OR = 0.39, 95% CI: 0.21-0.72). Results were consistent across lung cancer sub-types.Independent lines of evidence support an inverse association of elevated circulating IVC with lung cancer risk through a novel methodological approach that integrates genetic and traditional epidemiology to efficiently identify novel cancer biomarkers.Our results find compelling evidence in favor of a protective role for a circulating metabolite, IVC, in lung cancer aetiology. From the treatment of a Mendelian disease, isovaleric acidemia, we know that circulating IVC is modifiable through a restricted protein diet or glycine and L-carnatine supplementation. IVC may represent a modifiable and inversely associated biomarker for lung cancer.

Note: 2022 Oct 4;31(10):1966-1974

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Contributing Institute(s):

1. C020 Epidemiologie von Krebs (C020)

Research Program(s):

1. 313 - Krebsrisikofaktoren und Prävention (POF4-313) (POF4-313)

Appears in the scientific report 2022

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Essential Science Indicators ; IF < 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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