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Dietary and lifestyle determinants of acrylamide and glycidamide hemoglobin adducts in non-smoking postmenopausal women from the EPIC cohort

Abstract

Purpose

Acrylamide was classified as ‘probably carcinogenic’ to humans in 1994 by the International Agency for Research on Cancer. In 2002, public health concern increased when acrylamide was identified in starchy, plant-based foods, processed at high temperatures. The purpose of this study was to identify which food groups and lifestyle variables were determinants of hemoglobin adduct concentrations of acrylamide (HbAA) and glycidamide (HbGA) in 801 non-smoking postmenopausal women from eight countries in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

Methods

Biomarkers of internal exposure were measured in red blood cells (collected at baseline) by high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS) . In this cross-sectional analysis, four dependent variables were evaluated: HbAA, HbGA, sum of total adducts (HbAA + HbGA), and their ratio (HbGA/HbAA). Simple and multiple regression analyses were used to identify determinants of the four outcome variables. All dependent variables (except HbGA/HbAA) and all independent variables were log-transformed (log2) to improve normality. Median (25th–75th percentile) HbAA and HbGA adduct levels were 41.3 (32.8–53.1) pmol/g Hb and 34.2 (25.4–46.9) pmol/g Hb, respectively.

Results

The main food group determinants of HbAA, HbGA, and HbAA + HbGA were biscuits, crackers, and dry cakes. Alcohol intake and body mass index were identified as the principal determinants of HbGA/HbAA. The total percent variation in HbAA, HbGA, HbAA + HbGA, and HbGA/HbAA explained in this study was 30, 26, 29, and 13 %, respectively.

Conclusions

Dietary and lifestyle factors explain a moderate proportion of acrylamide adduct variation in non-smoking postmenopausal women from the EPIC cohort.

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References

  1. Friedman M (2003) Chemistry, biochemistry, and safety of acrylamide. A review. J Agric Food Chem 51:4504–4526

    CAS  Article  Google Scholar 

  2. Tareke E, Rydberg P, Karlsson P et al (2002) Analysis of acrylamide, a carcinogen formed in heated foodstuffs. J Agric Food Chem 50:4998–5006

    CAS  Article  Google Scholar 

  3. Becalski A, Brady B, Feng S et al (2011) Formation of acrylamide at temperatures lower than 100 °C: the case of prunes and a model study. Food Addit Contam Part A Chem Anal Control Expo Risk Assess 28:726–730. doi:10.1080/19440049.2010.535217

    CAS  Article  Google Scholar 

  4. Xu Y, Cui B, Ran R et al (2014) Risk assessment, formation, and mitigation of dietary acrylamide: current status and future prospects. Food Chem Toxicol 69C:1–12. doi:10.1016/j.fct.2014.03.037

    Article  Google Scholar 

  5. Freisling H, Moskal A, Ferrari P et al (2013) Dietary acrylamide intake of adults in the European Prospective Investigation into Cancer and Nutrition differs greatly according to geographical region. Eur J Nutr 52:1369–1380

    CAS  Article  Google Scholar 

  6. World Health Organization (2011) Evaluation of certain food additives and contaminants: seventy-second report of the joint FAO/WHO expert committee on food additives. World Health Organization Technical Report Series, No. 960, pp 1–115

  7. Zödl B, Schmid D, Wassler G et al (2007) Intestinal transport and metabolism of acrylamide. Toxicology 232:99–108. doi:10.1016/j.tox.2006.12.014

    Article  Google Scholar 

  8. LoPachin RM, Gavin T (2008) Acrylamide-induced nerve terminal damage: relevance to neurotoxic and neurodegenerative mechanisms. J Agric Food Chem 56:5994–6003

    CAS  Article  Google Scholar 

  9. IARC (1994) IARC working group on the evaluation of carcinogenic risks to humans: some industrial chemicals. Lyon, 15–22 February 1994. IARC Monogr Eval Carcinog Risks Hum 60:1–560

    Google Scholar 

  10. Fennell TR, Sumner SC, Walker VE (1992) A model for the formation and removal of hemoglobin adducts. Cancer Epidemiol Biomark Prev 1:213–219

    CAS  Google Scholar 

  11. Bergmark E (1997) Hemoglobin adducts of acrylamide and acrylonitrile in laboratory workers, smokers and nonsmokers. Chem Res Toxicol 10:78–84

    CAS  Article  Google Scholar 

  12. Vesper HW, Bernert JT, Ospina M et al (2007) Assessment of the relation between biomarkers for smoking and biomarkers for acrylamide exposure in humans. Cancer Epidemiol Biomark Prev 16:2471–2478

    CAS  Article  Google Scholar 

  13. EFSA Contam Panel (EFSA Panel on Contaminants in the Food Chain) (2015) Scientific opinion on acrylamide in food. EFSA J 13(6):4104. doi:10.2903/j.efsa.2015.4104

    Article  Google Scholar 

  14. Vesper HW, Slimani N, Hallmans G et al (2008) Cross-sectional study on acrylamide hemoglobin adducts in subpopulations from the European Prospective Investigation into Cancer and Nutrition (EPIC) Study. J Agric Food Chem 56:6046–6053

    CAS  Article  Google Scholar 

  15. Ferrari P, Freisling H, Duell EJ et al (2013) Challenges in estimating the validity of dietary acrylamide measurements. Eur J Nutr 52:1503–1512

    CAS  Article  Google Scholar 

  16. Bjellaas T, Olesen PT, Frandsen H et al (2007) Comparison of estimated dietary intake of acrylamide with hemoglobin adducts of acrylamide and glycidamide. Toxicol Sci 98:110–117

    CAS  Article  Google Scholar 

  17. Outzen M, Egeberg R, Dragsted L et al (2011) Dietary determinants for Hb-acrylamide and Hb-glycidamide adducts in Danish non-smoking women. Br J Nutr 105:1381–1387. doi:10.1017/S0007114510005003

    CAS  Article  Google Scholar 

  18. Wilson KM, Vesper HW, Tocco P et al (2009) Validation of a food frequency questionnaire measurement of dietary acrylamide intake using hemoglobin adducts of acrylamide and glycidamide. Cancer Causes Control 20:269–278

    Article  Google Scholar 

  19. Riboli E, Hunt KJ, Slimani N et al (2002) European Prospective Investigation into Cancer and Nutrition (EPIC): study populations and data collection. Public Health Nutr 5:1113–1124

    CAS  Article  Google Scholar 

  20. Obón-Santacana M, Freisling H, Peeters PH et al (2015) Acrylamide and glycidamide hemoglobin adduct levels and endometrial cancer risk: a nested case-control study in nonsmoking postmenopausal women from the EPIC cohort. Int J Cancer. doi:10.1002/ijc.29853

    Google Scholar 

  21. Obón-Santacana M, Lujan-Barroso L, Travis RC et al (2015) Acrylamide and glycidamide hemoglobin adducts and epithelial ovarian cancer: a nested case-control study in non-smoking postmenopausal women from the EPIC cohort. Cancer Epidemiol Biomark Prev. doi:10.1158/1055-9965.EPI-15-0822

    Google Scholar 

  22. Cust AE, Kaaks R, Friedenreich C et al (2007) Metabolic syndrome, plasma lipid, lipoprotein and glucose levels, and endometrial cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC). Endocr Relat Cancer 14:755–767. doi:10.1677/ERC-07-0132

    CAS  Article  Google Scholar 

  23. Peeters PH, Lukanova A, Allen N et al (2007) Serum IGF-I, its major binding protein (IGFBP-3) and epithelial ovarian cancer risk: the European Prospective Investigation into Cancer and Nutrition (EPIC). Endocr Relat Cancer 14:81–90

    CAS  Article  Google Scholar 

  24. Obon-Santacana M, Slimani N, Lujan-Barroso L et al (2013) Dietary intake of acrylamide and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Ann Oncol 24:2645–2651

    CAS  Article  Google Scholar 

  25. Vesper HW, Ospina M, Meyers T et al (2006) Automated method for measuring globin adducts of acrylamide and glycidamide at optimized Edman reaction conditions. Rapid Commun Mass Spectrom 20:959–964

    CAS  Article  Google Scholar 

  26. Schabacker J, Schwend T, Wink M (2004) Reduction of acrylamide uptake by dietary proteins in a Caco-2 gut model. J Agric Food Chem 52:4021–4025. doi:10.1021/jf035238w

    CAS  Article  Google Scholar 

  27. Wilson KM, Balter K, Adami HO et al (2009) Acrylamide exposure measured by food frequency questionnaire and hemoglobin adduct levels and prostate cancer risk in the Cancer of the Prostate in Sweden Study. Int J Cancer 124:2384–2390

    CAS  Article  Google Scholar 

  28. Willett W (2012) Nutritional epidemiology. Oxford University Press, Oxford

    Book  Google Scholar 

  29. Akaike H (1974) A new look at the statistical model identification. IEEE Trans Autom Control 19:716–723

    Article  Google Scholar 

  30. Wareham NJ, Jakes RW, Rennie KL et al (2003) Validity and repeatability of a simple index derived from the short physical activity questionnaire used in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Public Health Nutr 6:407–413

    Article  Google Scholar 

  31. McGraw KO, Wong SP (1996) Forming inferences about some intraclass correlation coefficients. Psychol Methods 1:30

    Article  Google Scholar 

  32. Kütting B, Uter W, Drexler H (2008) The association between self-reported acrylamide intake and hemoglobin adducts as biomarkers of exposure. Cancer Causes Control 19:273–281. doi:10.1007/s10552-007-9090-9

    Article  Google Scholar 

  33. Tran NL, Barraj LM, Murphy MM, Bi X (2010) Dietary acrylamide exposure and hemoglobin adducts—National Health and Nutrition Examination Survey (2003–04). Food Chem Toxicol 48:3098–3108. doi:10.1016/j.fct.2010.08.003

    CAS  Article  Google Scholar 

  34. Wirfalt E, Paulsson B, Tornqvist M et al (2008) Associations between estimated acrylamide intakes, and hemoglobin AA adducts in a sample from the Malmo Diet and Cancer cohort. Eur J Clin Nutr 62:314–323

    CAS  Article  Google Scholar 

  35. Xie Q, Liu Y, Sun H et al (2008) Inhibition of acrylamide toxicity in mice by three dietary constituents. J Agric Food Chem 56:6054–6060. doi:10.1021/jf0730542

    CAS  Article  Google Scholar 

  36. Vikstrom AC, Wilson KM, Paulsson B et al (2010) Alcohol influence on acrylamide to glycidamide metabolism assessed with hemoglobin-adducts and questionnaire data. Food Chem Toxicol 48:820–824

    Article  Google Scholar 

  37. Huang Y-F, Chen M-L, Liou S-H et al (2011) Association of CYP2E1, GST and mEH genetic polymorphisms with urinary acrylamide metabolites in workers exposed to acrylamide. Toxicol Lett 203:118–126. doi:10.1016/j.toxlet.2011.03.008

    CAS  Article  Google Scholar 

  38. Vesper HW, Sternberg MR, Frame T, Pfeiffer CM (2013) Among 10 sociodemographic and lifestyle variables, smoking is strongly associated with biomarkers of acrylamide exposure in a representative sample of the US population. J Nutr 143:995S–1000S

    CAS  Article  Google Scholar 

  39. Kotova N, Frostne C, Abramsson-Zetterberg L et al (2014) Differences in micronucleus frequency and acrylamide adduct levels with hemoglobin between vegetarians and non-vegetarians. Eur J Nutr. doi:10.1007/s00394-014-0796-7

    Google Scholar 

  40. Hogervorst JG, Baars BJ, Schouten LJ et al (2010) The carcinogenicity of dietary acrylamide intake: a comparative discussion of epidemiological and experimental animal research. Crit Rev Toxicol 40:485–512

    CAS  Article  Google Scholar 

  41. Hogervorst JG, Fortner RT, Mucci LA et al (2013) Associations between dietary acrylamide intake and plasma sex hormone levels. Cancer Epidemiol Biomark Prev 22:2024–2036

    CAS  Article  Google Scholar 

  42. Nagata C, Konishi K, Tamura T et al (2015) Associations of acrylamide intake with circulating levels of sex hormones and prolactin in premenopausal Japanese women. Cancer Epidemiol Biomark Prev 24:249–254. doi:10.1158/1055-9965.EPI-14-0935

    CAS  Article  Google Scholar 

  43. Powers SJ, Mottram DS, Curtis A, Halford NG (2013) Acrylamide concentrations in potato crisps in Europe from 2002 to 2011. Food Addit Contam Part A Chem Anal Control Expo Risk Assess 30:1493–1500. doi:10.1080/19440049.2013.805439

    CAS  Article  Google Scholar 

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Acknowledgments

This work was supported by the Wereld Kanker Onderzoek Fonds (WCRF NL) [Grant WCRF 2011/442] and by the Health Research Fund (FIS) of the Spanish Ministry of Health [Exp PI11/01473]. The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by the Health Research Fund (FIS) of the Spanish Ministry of Health, Regional Governments of Andalucía, Asturias, Basque Country, Murcia [no. 6236], Navarra and the Catalan Institute of Oncology, La Caixa [BM 06-130], Red Temática de Investigación Cooperativa en Cáncer [RD12/0036/0018; RD06/0020/0091] (Spain); Danish Cancer Society (Denmark); Ligue contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France); Deutsche Krebshilfe, Deutsches Krebsforschungszentrum (DKFZ) and Federal Ministry of Education and Research (Germany); the Hellenic Health Foundation (Greece); Associazione Italiana per la Ricerca sul Cancro (AIRC) and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), the Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF) and Statistics Netherlands (the Netherlands); Nordic Center of Excellence in Food, Nutrition and Health-Helga (Norway); Swedish Cancer Society, Swedish Scientific Council and Regional Government of Skåne and Västerbotten (Sweden); Cancer Research UK, Medical Research Council (United Kingdom). MO-S is affiliated with the University of Barcelona.

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Correspondence to Eric J. Duell.

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The authors declare that they have no conflict of interest. The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention.

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Obón-Santacana, M., Lujan-Barroso, L., Freisling, H. et al. Dietary and lifestyle determinants of acrylamide and glycidamide hemoglobin adducts in non-smoking postmenopausal women from the EPIC cohort. Eur J Nutr 56, 1157–1168 (2017). https://doi.org/10.1007/s00394-016-1165-5

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Keywords

  • Acrylamide
  • Glycidamide
  • Hemoglobin adducts
  • Biomarkers
  • Diet
  • Nutrition