@misc{10481/72760,
year = {2021},
month = {3},
url = {http://hdl.handle.net/10481/72760},
abstract = {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.},
organization = {Intramural Research Program of the National Cancer
Institute at the National Institutes of Health},
organization = {Cancer Research UK
C8221/A29017 and C8221/A19170},
organization = {Medical Research Council MR/M012190/1},
organization = {“Miguel Servet” program (CP15/00100) from the Institute of Health Carlos III (Cofunded
by the European Social Fund (ESF) - ESF investing in your future)},
organization = {French National Cancer Institute 2009-139 and 2014-1-RT-02-CIRC-1},
organization = {IARC funds},
publisher = {American Association for Cancer Research},
keywords = {Alcohol intake},
keywords = {Untargeted metabolomics},
keywords = {2-hydroxy-3-methylbutyric acid},
keywords = {Biomarkers},
keywords = {EPIC},
keywords = {ATBC},
title = {Novel biomarkers of habitual alcohol intake and associations with risk of pancreatic and liver cancers and liver disease mortality},
doi = {10.1101/2021.03.12.20224451},
author = {Loftfield, Erikka and Sánchez Pérez, María José},
}