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

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

doi:10.1093/jnci/djab078

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

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

Research output: Contribution to journal › Article › peer-review

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 = 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.

Original language	English
Pages (from-to)	1542-1550
Journal	Journal of the National Cancer Institute
Volume	113
Issue number	11
Early online date	2021 May 19
DOIs	https://doi.org/10.1093/jnci/djab078
Publication status	Published - 2021

Subject classification (UKÄ)

Cancer and Oncology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1093/jnci/djab078Licence: Unspecified

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Loftfield, E., Stepien, M., Viallon, V., Trijsburg, L., Rothwell, J. A., Robinot, N., Biessy, C., Bergdahl, I. A., Bodén, S., Schulze, M. B., Bergman, M., Weiderpass, E., Schmidt, J. A., Zamora-Ros, R., Nøst, T. H., Sandanger, T. M., Sonestedt, E., Ohlsson, B., Katzke, V., ... Ferrari, P. (2021). 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, 113(11), 1542-1550. https://doi.org/10.1093/jnci/djab078

@article{6fc62c8e9ca64c5698236bf2de6b467f,

title = "Novel Biomarkers of Habitual Alcohol Intake and Associations with Risk of Pancreatic and Liver Cancers and Liver Disease Mortality",

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 = 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.",

author = "Erikka Loftfield and Magdalena Stepien and Vivian Viallon and Laura Trijsburg and Rothwell, {Joseph A} and Nivonirina Robinot and Carine Biessy and Bergdahl, {Ingvar A} and Stina Bod{\'e}n and Schulze, {Matthias B} and Manuela Bergman and Elisabete Weiderpass and Schmidt, {Julie A} and Raul Zamora-Ros and N{\o}st, {Therese H} and Sandanger, {Torkjel M} and Emily Sonestedt and Bodil Ohlsson and Verena Katzke and Rudolf Kaaks and Fulvio Ricceri and Anne Tj{\o}nneland and Dahm, {Christina C} and Maria-Jose S{\'a}nchez and Antonia Trichopoulou and Rosario Tumino and Mar{\'i}a-Dolores Chirlaque and Giovanna Masala and Eva Ardanaz and Roel Vermeulen and Paul Brennan and Demetrius Albanes and Weinstein, {Stephanie J} and Augustin Scalbert and Freedman, {Neal D} and Gunter, {Marc J} and Mazda Jenab and Rashmi Sinha and Pekka Keski-Rahkonen and Pietro Ferrari",

year = "2021",

doi = "10.1093/jnci/djab078",

language = "English",

volume = "113",

pages = "1542--1550",

journal = "Journal of the National Cancer Institute",

issn = "1460-2105",

publisher = "Oxford University Press",

number = "11",

}

Loftfield, E, Stepien, M, Viallon, V, Trijsburg, L, Rothwell, JA, Robinot, N, Biessy, C, Bergdahl, IA, Bodén, S, Schulze, MB, Bergman, M, Weiderpass, E, Schmidt, JA, Zamora-Ros, R, Nøst, TH, Sandanger, TM, Sonestedt, E , Ohlsson, B, Katzke, V, Kaaks, R, Ricceri, F, Tjønneland, A, Dahm, CC, Sánchez, M-J, Trichopoulou, A, Tumino, R, Chirlaque, M-D, Masala, G, Ardanaz, E, Vermeulen, R, Brennan, P, Albanes, D, Weinstein, SJ, Scalbert, A, Freedman, ND, Gunter, MJ, Jenab, M, Sinha, R, Keski-Rahkonen, P & Ferrari, P 2021, '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, vol. 113, no. 11, pp. 1542-1550. https://doi.org/10.1093/jnci/djab078

TY - JOUR

T1 - Novel Biomarkers of Habitual Alcohol Intake and Associations with Risk of Pancreatic and Liver Cancers and Liver Disease Mortality

AU - Loftfield, Erikka

AU - Stepien, Magdalena

AU - Viallon, Vivian

AU - Trijsburg, Laura

AU - Rothwell, Joseph A

AU - Robinot, Nivonirina

AU - Biessy, Carine

AU - Bergdahl, Ingvar A

AU - Bodén, Stina

AU - Schulze, Matthias B

AU - Bergman, Manuela

AU - Weiderpass, Elisabete

AU - Schmidt, Julie A

AU - Zamora-Ros, Raul

AU - Nøst, Therese H

AU - Sandanger, Torkjel M

AU - Sonestedt, Emily

AU - Ohlsson, Bodil

AU - Katzke, Verena

AU - Kaaks, Rudolf

AU - Ricceri, Fulvio

AU - Tjønneland, Anne

AU - Dahm, Christina C

AU - Sánchez, Maria-Jose

AU - Trichopoulou, Antonia

AU - Tumino, Rosario

AU - Chirlaque, María-Dolores

AU - Masala, Giovanna

AU - Ardanaz, Eva

AU - Vermeulen, Roel

AU - Brennan, Paul

AU - Albanes, Demetrius

AU - Weinstein, Stephanie J

AU - Scalbert, Augustin

AU - Freedman, Neal D

AU - Gunter, Marc J

AU - Jenab, Mazda

AU - Sinha, Rashmi

AU - Keski-Rahkonen, Pekka

AU - Ferrari, Pietro

PY - 2021

Y1 - 2021

N2 - 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.

AB - 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.

U2 - 10.1093/jnci/djab078

DO - 10.1093/jnci/djab078

M3 - Article

C2 - 34010397

SN - 1460-2105

VL - 113

SP - 1542

EP - 1550

JO - Journal of the National Cancer Institute

JF - Journal of the National Cancer Institute

IS - 11

ER -

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

Abstract

Subject classification (UKÄ)

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