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Dietary antioxidant supplements and risk of keratinocyte cancers in women: a prospective cohort study

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Abstract

Purpose

Experimental studies suggested that antioxidants could protect against skin carcinomas. However, epidemiological studies on antioxidant supplement use in relation to basal-cell carcinoma (BCC) and squamous-cell carcinoma (SCC) risks yielded inconsistent findings, and few prospective studies have been conducted to date. We aimed to investigate the associations between antioxidant supplement intake and keratinocyte cancer (KC) risk.

Methods

E3N is an ongoing prospective cohort initiated in 1990 and involving 98,995 French women aged 40–65 years at recruitment. Intakes of dietary antioxidants were estimated via a validated dietary questionnaire in 1993 and self-reported antioxidant supplement use was collected in 1995. We used Cox models to compute hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for age and skin cancer risk factors.

Results

Over 1995–2014, 2426 BCC and 451 SCC cases were diagnosed among 63,063 women. We found positive relationships between vitamin A supplement use and KC risk (HR = 1.37, 95% CI 1.15–1.62), particularly with BCC (HR = 1.40, 95% CI 1.17–1.69); and between vitamin E supplement use and risks of both BCC (HR = 1.21, 95% CI 1.03–1.52) and SCC (HR = 1.43, 95% CI 1.03–1.99). Intake of beta-carotene supplements was associated with an increased SCC risk (HR = 1.59, 95% CI 1.00–2.54). Vitamin C supplement use was not associated with KC risk. We found similar results when considering total antioxidant intake.

Conclusions

Intakes of vitamin A or E supplements were associated with an increased KC risk in women. Further studies with information on doses and duration of supplement use and the ability to examine their underlying mechanisms are needed.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request. This manuscript contains original research and has not been previously published. However, preliminary findings from this work were presented as a communication at the 2020 Annual Meeting of the Society of Epidemiologic Research and the abstract was published with https://doi.org/10.1093/cdn/nzaa044_034.

Code availability

Code available on request from the authors.

Abbreviations

BCCs:

Basal-cell carcinomas

BMI:

Body mass index

CIs:

Confidence intervals

CNIL:

Commission nationale informatique et libertés

DNA:

Deoxyribonucleic acid

E3N:

Etude Epidemiologique auprès de femmes de l’Education Nationale

HR:

Hazard ratio

KCs:

Keratinocyte cancers

METs:

Metabolic equivalents of task

MGEN:

Mutuelle Générale de l’Education Nationale

SCCs:

Squamous-cell carcinomas

SD:

Standard deviation

UV:

Ultraviolet radiation

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Acknowledgements

We are grateful to all the women in the cohort for their continued participation and to the practitioners for providing pathology reports. We also thank all members of the E3N study group, particularly Rafika Chaït, Marie Fangon, Pascale Gerbouin-Rérolle, Sofiane Harizi, Lyan Hoang, Melody Enguix and Camille Laplanche for their technical assistance.

Funding

The E3N cohort from the French National Institute of Health and Medical Research (Inserm) was supported by the Mutuelle Générale de l’Education Nationale (MGEN); the Gustave Roussy Institute; and the French League against Cancer (LNCC). YMS was supported by the French National Institute of Health and Medical Research and MAR was supported by research scholarships from the French Ministry of Research.

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Author notes

  1. Yahya Mahamat-Saleh and Isabelle Savoye are co-first authors.

  2. Marie-Christine Boutron-Ruault and Marina Kvaskoff are co-last authors.

Authors and Affiliations

  1. Inserm U1018, “Exposome, Heredity, Cancer, and Health” Team, CESP, Paris-Saclay University, UVSQ, University Paris-Sud, Gustave Roussy, Espace Maurice Tubiana, 114 rue Edouard Vaillant, 94805, Villejuif Cedex, France

    Yahya Mahamat-Saleh, Iris Cervenka, Marie Al-Rahmoun, Claire Cadeau, Marie-Christine Boutron-Ruault & Marina Kvaskoff

  2. Belgian Health Care Knowledge Centre (KCE), Brussels, Belgium

    Isabelle Savoye

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Contributions

MK and MCBR conceived and designed the study. YM-S and IS performed the statistical analysis and YM-S drafted the manuscript. All authors contributed to the interpretation of data discussed in the manuscript, critically revised the manuscript, and approved its final version. MK is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Marina Kvaskoff.

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Conflict of interest

The authors have no conflict of interest to disclose.

Ethics approval

The E3N cohort was reviewed and approved by the French National Commission for Data Protection and Privacy (Commission Nationale Informatique et Libertés, CNIL). All women provided a signed informed consent prior to data collection.

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Mahamat-Saleh, Y., Savoye, I., Cervenka, I. et al. Dietary antioxidant supplements and risk of keratinocyte cancers in women: a prospective cohort study. Eur J Nutr 61, 2825–2836 (2022). https://doi.org/10.1007/s00394-022-02861-8

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