Novel Biomarkers of Habitual Alcohol Intake and Associations With Risk of Pancreatic and Liver Cancers and Liver Disease Mortality

Loftfield, Erikka; Stepien, Magdalena; Viallon, Vivian; Trijsburg, Laura; Rothwell, Joseph A.; Robinot, Nivonirina; Biessy, Carine; Bergdahl, Ingvar A.; Bodén, Stina; Schulze, Matthias B.; Bergman, Manuela; Weiderpass, Elisabete; Schmidt, Julie A.; Zamora-Ros, Raúl; Nøst, Therese Haugdahl; Sandanger, Torkjel M; Sonestedt, Emily; Ohlsson, Bodil; Katzke, Verena; Kaaks, Rudolf; Ricceri, Fulvio; Tjønneland, Anne; Dahm, Christina C.; Sánchez, Maria-Jose; Trichopoulou, Antonia; Tumino, Rosario; Chirlaque, María-Dolores; Masala, Giovanna; Ardanaz, Eva; Vermeulen, Roel; Brennan, P; Albanes, Demetrius; Weinstein, Stephanie J.; Scalbert, Augustin; Freedman, Neal D.; Gunter, Marc; Jenab, Mazda; Sinha, Rashmi; Keski-Rahkonen, Pekka; Ferrari, Pietro

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Date

2021-05-19

Type

Journal article
Tidsskriftartikkel

Abstract

Background - 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.

Methods - 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.

Results - 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.

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.

Citation

Loftfield, Stepien, Viallon, Trijsburg, Rothwell, Robinot, Biessy, Bergdahl, Bodén, Schulze, Bergman, Weiderpass, Schmidt, Zamora-Ros, Nøst, Sandanger, Sonestedt, Ohlsson, Katzke, Kaaks, Ricceri, Tjønneland, Dahm, Sánchez, Trichopoulou, Tumino, Chirlaque, Masala, Ardanaz, Vermeulen, Brennan, Albanes, Weinstein, Scalbert, Freedman, Gunter, Jenab, Sinha, Keski-Rahkonen, Ferrari. Novel Biomarkers of Habitual Alcohol Intake and Associations With Risk of Pancreatic and Liver Cancers and Liver Disease Mortality. Journal of the National Cancer Institute. 2021;113(11):1542-1550

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