Novel Biomarkers of Habitual Alcohol Intake and Associations With Risk of Pancreatic and Liver Cancers and Liver Disease Mortality-Reference-Cited by-全球学者库

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

Published:2021-05-19 Issue:11 Volume:113 Page:1542-1550
ISSN:0027-8874
Container-title:JNCI: Journal of the National Cancer Institute
language:en
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Author:

Loftfield Erikka¹^ORCID,Stepien Magdalena²^ORCID,Viallon Vivian³^ORCID,Trijsburg Laura³^ORCID,Rothwell Joseph A²⁴⁵^ORCID,Robinot Nivonirina⁶^ORCID,Biessy Carine³,Bergdahl Ingvar A⁷^ORCID,Bodén Stina⁸,Schulze Matthias B⁹¹⁰^ORCID,Bergman Manuela⁹¹⁰^ORCID,Weiderpass Elisabete¹¹,Schmidt Julie A¹²^ORCID,Zamora-Ros Raul¹³^ORCID,Nøst Therese H¹⁴,Sandanger Torkjel M¹⁴,Sonestedt Emily¹⁵^ORCID,Ohlsson Bodil¹⁵^ORCID,Katzke Verena¹⁶^ORCID,Kaaks Rudolf¹⁶^ORCID,Ricceri Fulvio¹⁷^ORCID,Tjønneland Anne¹⁸,Dahm Christina C¹⁹^ORCID,Sánchez Maria-Jose²⁰²¹²²,Trichopoulou Antonia²³^ORCID,Tumino Rosario²⁴^ORCID,Chirlaque María-Dolores²⁵²⁶^ORCID,Masala Giovanna²⁷^ORCID,Ardanaz Eva²⁸²⁹³⁰^ORCID,Vermeulen Roel³¹^ORCID,Brennan Paul³²,Albanes Demetrius¹^ORCID,Weinstein Stephanie J¹^ORCID,Scalbert Augustin⁶^ORCID,Freedman Neal D¹^ORCID,Gunter Marc J²^ORCID,Jenab Mazda²^ORCID,Sinha Rashmi¹^ORCID,Keski-Rahkonen Pekka⁶,Ferrari Pietro³^ORCID

Affiliation:

1. Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute,National Institutes of Health, Bethesda, MD, USA

2. Nutritional Epidemiology Group, International Agency for Research on Cancer (IARC-WHO), Lyon, France

3. Nutritional Methodology and Biostatistics Group, International Agency for Research on Cancer (IARC-WHO), Lyon, France

4. Gustave Roussy, F-94805, Villejuif, France

5. Biomarkers Group, International Agency for Research on Cancer (IARC-WHO), Lyon, France

6. Centre for Epidemiology and Population Health (U1018), Generations and Health team, Faculté de Médecine, Université Paris-Saclay, UVSQ, INSERM, Villejuif, France

7. Biobank Research Unit, Umeå University, Sweden

8. Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden

9. Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany

10. Institute of Nutritional Science, University of Potsdam, Nuthetal, Germany

11. International Agency for Research on Cancer, World Health Organization

12. Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK

13. Unit of Nutrition and Cancer, Epidemiology Research Program, Catalan Institute of Oncology, Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat, Barcelona, Spain

14. Department of Community Medicine, UiT- The Arctic University of Norway, Tromsø, Norway

15. Department of Clinical Sciences in Malmö, Lund University, Malmö, Sweden

16. Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany

17. Department of Clinical and Biological Sciences, University of Turin, Italy; Unit of Epidemiology, Regional Health Service ASL TO3, Grugliasco, TO, Italy

18. Danish Cancer Society Research Center; University of Copenhagen, Department of Public Health

19. Department of Public Health, Aarhus University, Denmark

20. Escuela Andaluza de Salud Pública (EASP), Granada, Spain; Instituto de Investigación Biosanitaria ibs. GRANADA, Granada, Spain

21. Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain

22. Department of Preventive Medicine and Public Health, University of Granada, Granada, Spain

23. Hellenic Health Foundation, Athens, Greece

24. Cancer Registry and Histopathology Department, Provincial Health Authority (ASP 7), Ragusa, Italy

25. Department of Epidemiology, Regional Health Council, IMIB-Arrixaca, Murcia University, Murcia, Spain

26. CIBER in Epidemiology and Public Health (CIBERESP), Madrid, Spain

27. Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network—ISPRO, Florence, Italy

28. Navarra Public Health Institute, Pamplona, Spain

29. IdiSNA, Navarra Institute for Health Research, Pamplona, Spain

30. CIBER Epidemiology and Public Health CIBERESP, Madrid, Spain

31. Institute for Risk Assessment Sciences, Division of Environmental Epidemiology, Utrecht University, Utrecht, the Netherlands

32. Genetic Epidemiology Group, International Agency for Research on Cancer (IARC-WHO), Lyon, France

Abstract

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.

Funder

International Agency for Research on Cancer

Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London

NIHR Imperial Biomedical Research Centre

Intramural Research Program of the National Cancer Institute at the National Institutes of Health

Cancer Research UK

Medical Research Council

“Miguel Servet”

Institute of Health Carlos III (Co-funded by the European Social Fund (ESF) - ESF investing in your future

Regional Governments of Andalucía, Asturias

Basque Country, Murcia and Navarra

Catalan Institute of Oncology