Citrus intake and risk of skin cancer in the European Prospective Investigation into Cancer and Nutrition cohort (EPIC)

Abstract

Citrus intake has been suggested to increase the risk of skin cancer. Although this relation is highly plausible biologically, epidemiologic evidence is lacking. We aimed to examine the potential association between citrus intake and skin cancer risk. EPIC is an ongoing multi-center prospective cohort initiated in 1992 and involving ~ 520,000 participants who have been followed-up in 23 centers from 10 European countries. Dietary data were collected at baseline using validated country-specific dietary questionnaires. We used Cox proportional hazards regression models to compute hazard ratios (HR) and 95% confidence intervals (CI). During a mean follow-up of 13.7 years, 8448 skin cancer cases were identified among 270,112 participants. We observed a positive linear dose–response relationship between total citrus intake and skin cancer risk (HR = 1.10, 95% CI 1.03–1.18 in the highest vs. lowest quartile; Ptrend = 0.001), particularly with basal cell carcinoma (BCC) (HR = 1.11, 95% CI 1.02–1.20, Ptrend = 0.007) and squamous cell carcinoma (SCC) (HR = 1.23, 95% CI 1.04–1.47, Ptrend = 0.01). Citrus fruit intake was positively associated with skin cancer risk (HR = 1.08, 95% CI 1.01–1.16, Ptrend = 0.01), particularly with melanoma (HR = 1.23, 95% CI 1.02–1.48; Ptrend = 0.01), although with no heterogeneity across skin cancer types (Phomogeneity = 0.21). Citrus juice was positively associated with skin cancer risk (Ptrend = 0.004), particularly with BCC (Ptrend = 0.008) and SCC (Ptrend = 0.004), but not with melanoma (Phomogeneity = 0.02). Our study suggests moderate positive linear dose–response relationships between citrus intake and skin cancer risk. Studies with available biomarker data and the ability to examine sun exposure behaviors are warranted to clarify these associations and examine the phototoxicity mechanisms of furocoumarin-rich foods.

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Abbreviations

BCCs:

Basal-cell carcinomas

BMI:

Body mass index

CIs:

Confidence intervals

E3N:

Etude Epidemiologique auprès de femmes de l’Education Nationale

EPIC:

European Prospective Investigation into Cancer and Nutrition

HPFS:

Health professionals follow-up study

HR:

Hazard ratio

IARC:

International Agency for Research on Cancer

KCs:

Keratinocyte cancers

METs:

Metabolic equivalents of task

NHS:

Nurses’ health study

PUVA:

Psoralen and ultraviolet radiation A radiation

SCCs:

Squamous-cell carcinomas

SD:

Standard deviation

UV:

Ultraviolet radiation

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Acknowledgements

We thank all study participants for their cooperation and all interviewers who participated in the fieldwork studies in each EPIC center. We also thank Bertrand Hemon at IARC for his valuable work and technical support with the EPIC database. IARC disclaimer: Where authors are identified as personnel of the International Agency for Research on Cancer/World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy or views of the International Agency for Research on Cancer/World Health Organization.

Funding

Yahya Mahamat-Saleh was supported by a research scholarship from the Paris Ile-de-France region. 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 Danish Cancer Society (Denmark); the French National Institute of Health and Medical Research (Inserm), the Mutuelle Générale de l’Education Nationale, the Gustave Roussy Institute, and the French League against Cancer (France); Deutsche Krebshilfe, Deutsches Krebsforschungszentrum (DKFZ); and Federal Ministry of Education and Research (Germany); Stavros Niarchos Foundation; the Hellenic Health Foundation; and Ministry of Health and Social Solidarity (Greece); Italian Association for Research on Cancer (AIRC); National Research Council; and AIRE-ONLUS Ragusa, AVIS Ragusa, Sicilian Government (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS); Netherlands Cancer Registry (NKR); LK Research Funds; Dutch Prevention Funds; Dutch ZON (Zorg Onderzoek Nederland); World Cancer Research Fund (WCRF); the National Institute for Public Health and the Environment (RIVM) and Statistics Netherlands (the Netherlands); European Research Council (ERC) (Grant Number ERC-2009-AdG 232997) and Nordforsk; and Nordic Center of Excellence Programme on Food, Nutrition and Health (Norway); Health Research Fund (FIS); Regional Governments of Andalucía, Asturias, Basque Country, Murcia (No. 6236) and Navarra; and ISCIII RETIC (RD06/0020) and the Catalan Institute of Oncology (Spain); Swedish Cancer Society; Swedish Scientific Council; and Regional Government of Skåne and Västerbotten (Sweden); Cancer Research UK (14136 to EPIC-Norfolk; C570/A16491 and C8221/A19170 for EPIC-Oxford); Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford); Stroke Association; British Heart Foundation; Department of Health; Food Standards Agency; and Wellcome Trust (UK). Reza Ghiasvand was supported by a grant (Project 6823329) from the Norwegian Cancer Society.

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Mahamat-Saleh, Y., Cervenka, I., Al-Rahmoun, M. et al. Citrus intake and risk of skin cancer in the European Prospective Investigation into Cancer and Nutrition cohort (EPIC). Eur J Epidemiol 35, 1057–1067 (2020). https://doi.org/10.1007/s10654-020-00666-9

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Keywords

  • Citrus
  • Cohort studies
  • Cutaneous melanoma
  • Epidemiology
  • Keratinocyte cancers