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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 LU ; Bodén, Stina and Schulze, Matthias B , et al. (2021) In Journal of the National Cancer Institute 113(11). p.1542-1550
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. 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 =... (More)

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. 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 = 1.51-4.27) and pancreatic cancer (OR = 1.43; 95% CI = 1.03-1.99) in EPIC and liver cancer (OR = 2.00; 95% CI = 1.44-2.77) and liver disease mortality (OR = 2.16; 95% CI = 1.63-2.86) 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 = 1.60-2.98) 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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of the National Cancer Institute
volume
113
issue
11
pages
1542 - 1550
publisher
Oxford University Press
external identifiers
  • scopus:85121055459
  • pmid:34010397
ISSN
1460-2105
DOI
10.1093/jnci/djab078
language
English
LU publication?
yes
id
6fc62c8e-9ca6-4c56-9823-6bf2de6b467f
date added to LUP
2021-08-11 14:55:53
date last changed
2022-10-02 17:36:55
@article{6fc62c8e-9ca6-4c56-9823-6bf2de6b467f,
  abstract     = {{<p>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. Biomarkers of habitual alcohol intake may provide novel insight into the relationship between alcohol and cancer risk.</p><p>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.</p><p>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 = 1.51-4.27) and pancreatic cancer (OR = 1.43; 95% CI = 1.03-1.99) in EPIC and liver cancer (OR = 2.00; 95% CI = 1.44-2.77) and liver disease mortality (OR = 2.16; 95% CI = 1.63-2.86) 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 = 1.60-2.98) in ATBC.</p><p>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.</p>}},
  author       = {{Loftfield, Erikka and Stepien, Magdalena and Viallon, Vivian and Trijsburg, Laura and Rothwell, Joseph A and Robinot, Nivonirina and Biessy, Carine and Bergdahl, Ingvar A and Bodén, Stina and Schulze, Matthias B and Bergman, Manuela and Weiderpass, Elisabete and Schmidt, Julie A and Zamora-Ros, Raul and Nøst, Therese H and Sandanger, Torkjel M and Sonestedt, Emily and Ohlsson, Bodil and Katzke, Verena and Kaaks, Rudolf and Ricceri, Fulvio and Tjønneland, Anne and Dahm, Christina C and Sánchez, Maria-Jose and Trichopoulou, Antonia and Tumino, Rosario and Chirlaque, María-Dolores and Masala, Giovanna and Ardanaz, Eva and Vermeulen, Roel and Brennan, Paul and Albanes, Demetrius and Weinstein, Stephanie J and Scalbert, Augustin and Freedman, Neal D and Gunter, Marc J and Jenab, Mazda and Sinha, Rashmi and Keski-Rahkonen, Pekka and Ferrari, Pietro}},
  issn         = {{1460-2105}},
  language     = {{eng}},
  month        = {{05}},
  number       = {{11}},
  pages        = {{1542--1550}},
  publisher    = {{Oxford University Press}},
  series       = {{Journal of the National Cancer Institute}},
  title        = {{Novel Biomarkers of Habitual Alcohol Intake and Associations with Risk of Pancreatic and Liver Cancers and Liver Disease Mortality}},
  url          = {{http://dx.doi.org/10.1093/jnci/djab078}},
  doi          = {{10.1093/jnci/djab078}},
  volume       = {{113}},
  year         = {{2021}},
}