%0 Journal Article
%A Loftfield, Erikka
%A Stepien, Magdalena
%A Viallon, Vivian
%A Trijsburg, Laura
%A Rothwell, Joseph A
%A Robinot, Nivonirina
%A Biessy, Carine
%A Bergdahl, Ingvar A
%A Bodén, Stina
%A Schulze, Matthias B
%A Bergman, Manuela
%A Weiderpass, Elisabete
%A Schmidt, Julie A
%A Zamora-Ros, Raul
%A Nøst, Therese H
%A Sandanger, Torkjel M
%A Sonestedt, Emily
%A Ohlsson, Bodil
%A Katzke, Verena
%A Kaaks, Rudolf
%A Ricceri, Fulvio
%A Tjønneland, Anne
%A Dahm, Christina C
%A Sánchez, Maria-Jose
%A Trichopoulou, Antonia
%A Tumino, Rosario
%A Chirlaque, María-Dolores
%A Masala, Giovanna
%A Ardanaz, Eva
%A Vermeulen, Roel
%A Brennan, Paul
%A Albanes, Demetrius
%A Weinstein, Stephanie J
%A Scalbert, Augustin
%A Freedman, Neal D
%A Gunter, Marc J
%A Jenab, Mazda
%A Sinha, Rashmi
%A Keski-Rahkonen, Pekka
%A Ferrari, Pietro
%T Novel Biomarkers of Habitual Alcohol Intake and Associations With Risk of Pancreatic and Liver Cancers and Liver Disease Mortality.
%D 2021
%U https://hdl.handle.net/10668/24660
%X Alcohol is an established risk factor for several cancers, but modest alcohol-cancer associations may be missed because of measurement error in self-reported assessments. Biomarkers of habitual alcohol intake may provide novel insight into the relationship between alcohol and cancer risk. Untargeted metabolomics was used to identify metabolites correlated with self-reported habitual alcohol intake in a discovery dataset from the European Prospective Investigation into Cancer and Nutrition (EPIC; n = 454). Statistically significant correlations were tested in independent datasets of controls from case-control studies nested within EPIC (n = 280) and the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC; n = 438) study. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations of alcohol-associated metabolites and self-reported alcohol intake with risk of pancreatic cancer, hepatocellular carcinoma (HCC), liver cancer, and liver disease mortality in the contributing studies. Two metabolites displayed a dose-response association with self-reported alcohol intake: 2-hydroxy-3-methylbutyric acid and an unidentified compound. A 1-SD (log2) increase in levels of 2-hydroxy-3-methylbutyric acid was associated with risk of HCC (OR = 2.54, 95% CI = 1.51 to 4.27) and pancreatic cancer (OR = 1.43, 95% CI = 1.03 to 1.99) in EPIC and liver cancer (OR = 2.00, 95% CI = 1.44 to 2.77) and liver disease mortality (OR = 2.16, 95% CI = 1.63 to 2.86) in ATBC. Conversely, a 1-SD (log2) increase in 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, 95% CI = 1.60 to 2.98) in ATBC. 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.
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