Lung cancer metabolomics: a pooled analysis in the Cancer Prevention Studies.
BMC Med
; 22(1): 262, 2024 Jun 24.
Article
em En
| MEDLINE
| ID: mdl-38915026
ABSTRACT
BACKGROUND:
A better understanding of lung cancer etiology and the development of screening biomarkers have important implications for lung cancer prevention.METHODS:
We included 623 matched case-control pairs from the Cancer Prevention Study (CPS) cohorts. Pre-diagnosis blood samples were collected between 1998 and 2001 in the CPS-II Nutrition cohort and 2006 and 2013 in the CPS-3 cohort and were sent for metabolomics profiling simultaneously. Cancer-free controls at the time of case diagnosis were 11 matched to cases on date of birth, blood draw date, sex, and race/ethnicity. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using conditional logistic regression, controlling for confounders. The Benjamini-Hochberg method was used to correct for multiple comparisons.RESULTS:
Sphingomyelin (d180/220) (OR 1.32; 95% CI 1.15, 1.53, FDR = 0.15) and taurodeoxycholic acid 3-sulfate (OR 1.33; 95% CI 1.14, 1.55, FDR = 0.15) were positively associated with lung cancer risk. Participants diagnosed within 3 years of blood draw had a 55% and 48% higher risk of lung cancer per standard deviation increase in natural log-transformed sphingomyelin (d180/220) and taurodeoxycholic acid 3-sulfate level, while 26% and 28% higher risk for those diagnosed beyond 3 years, compared to matched controls. Lipid and amino acid metabolism accounted for 47% to 80% of lung cancer-associated metabolites at P < 0.05 across all participants and subgroups. Notably, ever-smokers exhibited a higher proportion of lung cancer-associated metabolites (P < 0.05) in xenobiotic- and lipid-associated pathways, whereas never-smokers showed a more pronounced involvement of amino acid- and lipid-associated metabolic pathways.CONCLUSIONS:
This is the largest prospective study examining untargeted metabolic profiles regarding lung cancer risk. Sphingomyelin (d180/220), a sphingolipid, and taurodeoxycholic acid 3-sulfate, a bile salt, may be risk factors and potential screening biomarkers for lung cancer. Lipid and amino acid metabolism may contribute significantly to lung cancer etiology which varied by smoking status.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Metabolômica
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Neoplasias Pulmonares
Limite:
Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article