Ultra-processed foods, adiposity and risk of head and neck cancer and oesophageal adenocarcinoma in the European Prospective Investigation into Cancer and Nutrition study: a mediation analysis

doi:10.1007/s00394-023-03270-1

. 2024 Mar;63(2):377-396.

doi: 10.1007/s00394-023-03270-1. Epub 2023 Nov 22.

Ultra-processed foods, adiposity and risk of head and neck cancer and oesophageal adenocarcinoma in the European Prospective Investigation into Cancer and Nutrition study: a mediation analysis

Fernanda Morales-Berstein^{1

2}, Carine Biessy³, Vivian Viallon³, Ana Goncalves-Soares^{4

5}, Corinne Casagrande³, Bertrand Hémon³, Nathalie Kliemann^{3

6}, Manon Cairat^{3

7}, Jessica Blanco Lopez³, Aline Al Nahas³, Kiara Chang⁸, Eszter Vamos⁸, Fernanda Rauber^{9

10}, Renata Bertazzi Levy^{9

10}, Diana Barbosa Cunha¹¹, Paula Jakszyn^{12

13

14}, Pietro Ferrari³, Paolo Vineis^{15

16}, Giovanna Masala¹⁷, Alberto Catalano¹⁸, Emily Sonestedt¹⁹, Yan Borné¹⁹, Verena Katzke²⁰, Rashmita Bajracharya²⁰, Claudia Agnoli²¹, Marcela Guevara^{22

23

24}, Alicia Heath²⁵, Loredana Radoï⁷, Francesca Mancini⁷, Elisabete Weiderpass²⁶, José María Huerta^{23

27}, María-José Sánchez^{23

28

29

30}, Anne Tjønneland^{31

32}, Cecilie Kyrø³¹, Matthias B Schulze^{33

34}, Guri Skeie³⁵, Marko Lukic³⁵, Tonje Braaten³⁵, Marc Gunter^{3

25}, Christopher Millett^{8

36}, Antonio Agudo^{12

13}, Paul Brennan³⁷, M Carolina Borges^{4

5}, Rebecca C Richmond^{4

5}, Tom G Richardson^{4

5}, George Davey Smith^{4

5}, Caroline L Relton^{4

5}, Inge Huybrechts³; EPIC Network

Affiliations

¹ MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK. dy20206@bristol.ac.uk.
² Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK. dy20206@bristol.ac.uk.
³ Nutrition and Metabolism Branch, International Agency for Research on Cancer/World Health Organization, Lyon, France.
⁴ MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
⁵ Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
⁶ Cancer Research Center of Santa Catarina, CEPON, Florianópolis, Brazil.
⁷ Paris-Saclay University, UVSQ, Inserm "Exposome, Heredity, Cancer and Health" Team, CESP U1018, Gustave Roussy, Villejuif, France.
⁸ Public Health Policy Evaluation Unit, School of Public Health, Imperial College London, London, UK.
⁹ Preventive Medicine Department of the Medical School, University of São Paulo, São Paulo, Brazil.
¹⁰ Center for Epidemiological Research in Nutrition and Health, University of São Paulo, São Paulo, Brazil.
¹¹ Hésio Cordeiro Institute of Social Medicine, Department of Epidemiology, Rio de Janeiro State University, Rio de Janeiro, RJ, Brazil.
¹² Unit of Nutrition and Cancer, Catalan Institute of Oncology-ICO, L'Hospitalet de Llobregat, Spain.
¹³ Nutrition and Cancer Group; Epidemiology, Public Health, Cancer Prevention and Palliative Care Program, Bellvitge Biomedical Research Institute-IDIBELL, L'Hospitalet de Llobregat, Spain.
¹⁴ Blanquerna Faculty of Health Sciences, Ramon Llull University, Barcelona, Spain.
¹⁵ MRC Centre for Environment and Health, School of Public Health, Imperial College London, Norfolk Place, London, W2 1PG, UK.
¹⁶ Italian Institute of Technology, Genoa, Italy.
¹⁷ Institute for Cancer Research, Prevention and Clinical Network (ISPRO), Florence, Italy.
¹⁸ Centre for Biostatistics, Epidemiology, and Public Health, Department of Clinical and Biological Sciences, University of Turin, 10043, Orbassano, TO, Italy.
¹⁹ Nutrition Epidemiology, Department of Clinical Sciences Malmö, Faculty of Medicine, Lund University, Lund, Sweden.
²⁰ Department of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
²¹ Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
²² Instituto de Salud Pública y Laboral de Navarra, 31003, Pamplona, Spain.
²³ Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), 28029, Madrid, Spain.
²⁴ Navarra Institute for Health Research (IdiSNA), 31008, Pamplona, Spain.
²⁵ Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
²⁶ International Agency for Research on Cancer, World Health Organization, Lyon, France.
²⁷ Department of Epidemiology, Murcia Regional Health Council-IMIB, Murcia, Spain.
²⁸ Escuela Andaluza de Salud Pública (EASP), 18011, Granada, Spain.
²⁹ Instituto de Investigación Biosanitaria ibs.GRANADA, 18012, Granada, Spain.
³⁰ Department of Preventive Medicine and Public Health, University of Granada, 18071, Granada, Spain.
³¹ Danish Cancer Society Research Center, Diet, Cancer and Health, Strandboulevarden 49, DK-2100, Copenhagen, Denmark.
³² Department of Public Health, University of Copenhagen, DK-2200, Copenhagen, Denmark.
³³ Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.
³⁴ Institute of Nutritional Science, University of Potsdam, Nuthetal, Germany.
³⁵ Department of Community Medicine, Faculty of Health Sciences, UiT The Arctic University of Norway, Tromsø, Norway.
³⁶ NOVA National School of Public Health, Public Health Research Centre, Comprehensive Health Research Center, CHRC, NOVA University Lisbon, Lisbon, Portugal.
³⁷ Genetic Epidemiology Group, International Agency for Research on Cancer, World Health Organization, Lyon, France.

PMID: 37989797
PMCID: PMC10899298
DOI: 10.1007/s00394-023-03270-1

Ultra-processed foods, adiposity and risk of head and neck cancer and oesophageal adenocarcinoma in the European Prospective Investigation into Cancer and Nutrition study: a mediation analysis

Fernanda Morales-Berstein et al. Eur J Nutr. 2024 Mar.

. 2024 Mar;63(2):377-396.

doi: 10.1007/s00394-023-03270-1. Epub 2023 Nov 22.

Authors

Affiliations

¹ MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK. dy20206@bristol.ac.uk.
² Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK. dy20206@bristol.ac.uk.
³ Nutrition and Metabolism Branch, International Agency for Research on Cancer/World Health Organization, Lyon, France.
⁴ MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
⁵ Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
⁶ Cancer Research Center of Santa Catarina, CEPON, Florianópolis, Brazil.
⁷ Paris-Saclay University, UVSQ, Inserm "Exposome, Heredity, Cancer and Health" Team, CESP U1018, Gustave Roussy, Villejuif, France.
⁸ Public Health Policy Evaluation Unit, School of Public Health, Imperial College London, London, UK.
⁹ Preventive Medicine Department of the Medical School, University of São Paulo, São Paulo, Brazil.
¹⁰ Center for Epidemiological Research in Nutrition and Health, University of São Paulo, São Paulo, Brazil.
¹¹ Hésio Cordeiro Institute of Social Medicine, Department of Epidemiology, Rio de Janeiro State University, Rio de Janeiro, RJ, Brazil.
¹² Unit of Nutrition and Cancer, Catalan Institute of Oncology-ICO, L'Hospitalet de Llobregat, Spain.
¹³ Nutrition and Cancer Group; Epidemiology, Public Health, Cancer Prevention and Palliative Care Program, Bellvitge Biomedical Research Institute-IDIBELL, L'Hospitalet de Llobregat, Spain.
¹⁴ Blanquerna Faculty of Health Sciences, Ramon Llull University, Barcelona, Spain.
¹⁵ MRC Centre for Environment and Health, School of Public Health, Imperial College London, Norfolk Place, London, W2 1PG, UK.
¹⁶ Italian Institute of Technology, Genoa, Italy.
¹⁷ Institute for Cancer Research, Prevention and Clinical Network (ISPRO), Florence, Italy.
¹⁸ Centre for Biostatistics, Epidemiology, and Public Health, Department of Clinical and Biological Sciences, University of Turin, 10043, Orbassano, TO, Italy.
¹⁹ Nutrition Epidemiology, Department of Clinical Sciences Malmö, Faculty of Medicine, Lund University, Lund, Sweden.
²⁰ Department of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
²¹ Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
²² Instituto de Salud Pública y Laboral de Navarra, 31003, Pamplona, Spain.
²³ Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), 28029, Madrid, Spain.
²⁴ Navarra Institute for Health Research (IdiSNA), 31008, Pamplona, Spain.
²⁵ Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
²⁶ International Agency for Research on Cancer, World Health Organization, Lyon, France.
²⁷ Department of Epidemiology, Murcia Regional Health Council-IMIB, Murcia, Spain.
²⁸ Escuela Andaluza de Salud Pública (EASP), 18011, Granada, Spain.
²⁹ Instituto de Investigación Biosanitaria ibs.GRANADA, 18012, Granada, Spain.
³⁰ Department of Preventive Medicine and Public Health, University of Granada, 18071, Granada, Spain.
³¹ Danish Cancer Society Research Center, Diet, Cancer and Health, Strandboulevarden 49, DK-2100, Copenhagen, Denmark.
³² Department of Public Health, University of Copenhagen, DK-2200, Copenhagen, Denmark.
³³ Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.
³⁴ Institute of Nutritional Science, University of Potsdam, Nuthetal, Germany.
³⁵ Department of Community Medicine, Faculty of Health Sciences, UiT The Arctic University of Norway, Tromsø, Norway.
³⁶ NOVA National School of Public Health, Public Health Research Centre, Comprehensive Health Research Center, CHRC, NOVA University Lisbon, Lisbon, Portugal.
³⁷ Genetic Epidemiology Group, International Agency for Research on Cancer, World Health Organization, Lyon, France.

PMID: 37989797
PMCID: PMC10899298
DOI: 10.1007/s00394-023-03270-1

Abstract

Purpose: To investigate the role of adiposity in the associations between ultra-processed food (UPF) consumption and head and neck cancer (HNC) and oesophageal adenocarcinoma (OAC) in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

Methods: Our study included 450,111 EPIC participants. We used Cox regressions to investigate the associations between the consumption of UPFs and HNC and OAC risk. A mediation analysis was performed to assess the role of body mass index (BMI) and waist-to-hip ratio (WHR) in these associations. In sensitivity analyses, we investigated accidental death as a negative control outcome.

Results: During a mean follow-up of 14.13 ± 3.98 years, 910 and 215 participants developed HNC and OAC, respectively. A 10% g/d higher consumption of UPFs was associated with an increased risk of HNC (hazard ratio [HR] = 1.23, 95% confidence interval [CI] 1.14-1.34) and OAC (HR = 1.24, 95% CI 1.05-1.47). WHR mediated 5% (95% CI 3-10%) of the association between the consumption of UPFs and HNC risk, while BMI and WHR, respectively, mediated 13% (95% CI 6-53%) and 15% (95% CI 8-72%) of the association between the consumption of UPFs and OAC risk. UPF consumption was positively associated with accidental death in the negative control analysis.

Conclusions: We reaffirmed that higher UPF consumption is associated with greater risk of HNC and OAC in EPIC. The proportion mediated via adiposity was small. Further research is required to investigate other mechanisms that may be at play (if there is indeed any causal effect of UPF consumption on these cancers).

Keywords: Adiposity; Epidemiology; Food processing; Head and neck cancer; Mediation analysis; NOVA classification; Oesophageal cancer.

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Conflict of interest statement

Financial interests: TGR is an employee of GlaxoSmithKline outside of this research. The rest of the authors have no financial interests to disclose. Non-financial interests: The authors have no non-financial interests to declare. The authors declare that no funds, grants or other support were received during the preparation of this manuscript.

Figures

**Fig. 1**
Mediation analysis diagram of the counterfactual two-way decomposition of the total effect of UPF consumption on the risk of head and neck cancer and oesophageal adenocarcinoma. All mediation models accounted for potential exposure–mediator interactions and were adjusted for age at recruitment in 1-year categories, sex, sub-centre, education, physical activity, height, smoking status and alcohol intake. The total effect (TE) corresponds to the sum of the pure natural direct effect (PNDE) and the total natural indirect effect (TNIE). Point estimates were obtained by direct counterfactual imputation estimation and confidence intervals were obtained using 1000 bootstrap repetitions. Abbreviations: BMI, body mass index; WHR, waist-to-hip ratio; UPF, ultra-processed food; HNC, head and neck cancer, OAC, oesophageal adenocarcinoma

**Fig. 2**
Associations between the consumption of ultra-processed foods (in %g/d) and the risk of head and neck cancer and oesophageal adenocarcinoma. Hazard ratios per 10% g/d higher ultra-processed food intake. Time of entry was defined as age at recruitment, while time of exit was defined as age at first cancer diagnosis (excluding non-melanoma skin cancer) or age at last follow-up (i.e. death, emigration, loss to follow-up or end of follow-up), whichever came first. Model 1 was stratified by age at recruitment in 1-year categories, sex, and sub-centre. Model 2 was additionally adjusted for education, physical activity, height, and smoking status. Model 3 was additionally adjusted for alcohol intake. N = 450,111, of which 910 and 215 had head and neck cancer and oesophageal adenocarcinoma, respectively. Abbreviations: CI, confidence interval; UPF, ultra-processed food

**Fig. 3**
Associations between the consumption of ultra-processed foods (in %g/d) and head and neck cancer subtypes. Hazard ratios per 10% g/d higher ultra-processed food intake. Time of entry was defined as age at recruitment, while time of exit was defined as age at first cancer diagnosis (excluding non-melanoma skin cancer) or age at last follow-up (i.e. death, emigration, loss to follow-up or end of follow-up), whichever came first. Model 1 was stratified by age at recruitment in 1-year categories, sex, and sub-centre. Model 2 was additionally adjusted for education, physical activity, height and smoking status. Model 3 was additionally adjusted for alcohol intake. N = 450,111, of which 234, 235, 66, 310 and 65 had cancer of the oral cavity, oropharynx, hypopharynx, larynx, and oral cavity and pharynx unspecified/overlapping regions, respectively. Abbreviations: CI, confidence interval; UPF, ultra-processed food

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References

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1. Monteiro CA, Cannon G, Levy RB, et al. Ultra-processed foods: what they are and how to identify them. Public Health Nutr. 2019;22(5):936–941. doi: 10.1017/S1368980018003762. - DOI - PMC - PubMed
1. Monteiro CA, Cannon G, Levy RB, et al. The food system ultra-processing. the big issue for nutrition, disease, health, well-being. World Nutr J World Public Heal Nutr Assoc. 2012;3(12):527–569.
1. Monteiro CA, Levy RB, Claro RM, et al. Increasing consumption of ultra-processed foods and likely impact on human health: evidence from Brazil. Public Health Nutr. 2011;14(1):5–13. doi: 10.1017/S1368980010003241. - DOI - PubMed
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[1] Monteiro CA, Levy RB, Claro RM, et al. A new classification of foods based on the extent and purpose of their processing. Cad Saude Publica. 2010;26(11):2039–2049. doi: 10.1590/S0102-311X2010001100005. - DOI - PubMed

[2] Monteiro CA, Levy RB, Claro RM, et al. A new classification of foods based on the extent and purpose of their processing. Cad Saude Publica. 2010;26(11):2039–2049. doi: 10.1590/S0102-311X2010001100005. - DOI - PubMed

[3] Monteiro CA, Cannon G, Levy RB, et al. Ultra-processed foods: what they are and how to identify them. Public Health Nutr. 2019;22(5):936–941. doi: 10.1017/S1368980018003762. - DOI - PMC - PubMed

[4] Monteiro CA, Cannon G, Levy RB, et al. Ultra-processed foods: what they are and how to identify them. Public Health Nutr. 2019;22(5):936–941. doi: 10.1017/S1368980018003762. - DOI - PMC - PubMed

[5] Monteiro CA, Cannon G, Levy RB, et al. The food system ultra-processing. the big issue for nutrition, disease, health, well-being. World Nutr J World Public Heal Nutr Assoc. 2012;3(12):527–569.

[6] Monteiro CA, Cannon G, Levy RB, et al. The food system ultra-processing. the big issue for nutrition, disease, health, well-being. World Nutr J World Public Heal Nutr Assoc. 2012;3(12):527–569.

[7] Monteiro CA, Levy RB, Claro RM, et al. Increasing consumption of ultra-processed foods and likely impact on human health: evidence from Brazil. Public Health Nutr. 2011;14(1):5–13. doi: 10.1017/S1368980010003241. - DOI - PubMed

[8] Monteiro CA, Levy RB, Claro RM, et al. Increasing consumption of ultra-processed foods and likely impact on human health: evidence from Brazil. Public Health Nutr. 2011;14(1):5–13. doi: 10.1017/S1368980010003241. - DOI - PubMed

[9] Fiolet T, Srour B, Sellem L, et al. Consumption of ultra-processed foods and cancer risk: results from NutriNet-Sante prospective cohort. BMJ. 2018;360:k322. doi: 10.1136/bmj.k322. - DOI - PMC - PubMed

[10] Fiolet T, Srour B, Sellem L, et al. Consumption of ultra-processed foods and cancer risk: results from NutriNet-Sante prospective cohort. BMJ. 2018;360:k322. doi: 10.1136/bmj.k322. - DOI - PMC - PubMed

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Ultra-processed foods, adiposity and risk of head and neck cancer and oesophageal adenocarcinoma in the European Prospective Investigation into Cancer and Nutrition study: a mediation analysis

Affiliations

Ultra-processed foods, adiposity and risk of head and neck cancer and oesophageal adenocarcinoma in the European Prospective Investigation into Cancer and Nutrition study: a mediation analysis

Authors

Affiliations

Abstract

Conflict of interest statement

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