Novel biomarkers of habitual alcohol intake and associations with risk of pancreatic and liver cancers and liver disease mortality
Metadatos
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American Association for Cancer Research
Materia
Alcohol intake Untargeted metabolomics 2-hydroxy-3-methylbutyric acid Biomarkers EPIC ATBC
Fecha
2021-03-15Referencia bibliográfica
Published version: Loftfield, E... [et al.]. Novel biomarkers of habitual alcohol intake and associations with risk of pancreatic and liver cancers and liver disease mortality. Cancer Res July 1 2021 (81) (13 Supplement) 747; DOI: [10.1158/1538-7445.AM2021-747]
Patrocinador
Intramural Research Program of the National Cancer Institute at the National Institutes of Health; Cancer Research UK C8221/A29017 and C8221/A19170; Medical Research Council MR/M012190/1; “Miguel Servet” program (CP15/00100) from the Institute of Health Carlos III (Cofunded by the European Social Fund (ESF) - ESF investing in your future); French National Cancer Institute 2009-139 and 2014-1-RT-02-CIRC-1; IARC fundsResumen
Background: Alcohol is an established risk factor for several cancers, but modest alcohol-cancer
associations may be missed due to measurement error in self-reported assessments. The identification
of biomarkers of habitual alcohol intake may enhance evidence on the role of alcohol in cancer onset.
Methods: Untargeted metabolomics was used to identify metabolites correlated with habitual alcohol
intake in a discovery dataset from the European Prospective Investigation into Cancer and Nutrition
(EPIC; n=454). Significant correlations were replicated in independent datasets of controls from casecontrol
studies nested within EPIC (n=281) and the Alpha-Tocopherol, Beta-Carotene Cancer
Prevention (ATBC; n=438) study. Conditional logistic regression was used to estimate odds ratios
(OR) and 95% confidence intervals for associations of alcohol-associated metabolites and selfreported
alcohol intake with risk of pancreatic cancer, hepatocellular carcinoma (HCC), liver cancer,
and liver disease mortality in the contributing studies.
Results: Two metabolites displayed a dose-response association with alcohol intake: 2-hydroxy-3-
methylbutyric acid and an unidentified compound (m/z(+):231.0839). A 1-SD increase in log2-
transformed levels of 2-hydroxy-3-methylbutyric acid was associated with risk of HCC (OR=2.14;
1.39-3.31) and pancreatic cancer (OR=1.65; 1.17-2.32) in EPIC and liver cancer (OR=2.00; 1.44-2.77)
and liver disease mortality (OR=2.16; 1.63-2.86) in ATBC. Conversely, a 1-SD increase in log2-
transformed questionnaire-derived alcohol intake was not associated with HCC or pancreatic cancer in
EPIC or liver cancer in ATBC but was associated with liver disease mortality (OR=2.19; 1.60-2.98) in
ATBC.
Conclusions: 2-Hydroxy-3-methylbutyric acid is a candidate biomarker of habitual alcohol intake that
may advance the study of alcohol and cancer risk in population-based studies.