The Association Between Citrus Consumption and Melanoma Risk in the UK Biobank

A.R. Marley; M. Li; V.L. Champion; Y. Song; J. Han; X. Li

Disclosures

The British Journal of Dermatology. 2021;185(2):353-362. 

In This Article

Abstract and Introduction

Abstract

Background: Melanoma incidence has been dramatically increasing worldwide. Psoralen, a known photocarcinogen, is naturally abundant in citrus products, leading to the hypothesis that high citrus consumption may increase melanoma risk.

Objectives: To investigate the association between total citrus consumption and melanoma risk, and the association between individual citrus products and melanoma risk, and to test for interactions between total citrus intake and established melanoma risk factors.

Methods: Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between citrus consumption and melanoma risk among 1592 cases and 197 372 controls from the UK Biobank cohort. Citrus consumption data were collected via five rounds of 24-h recall questionnaires. International Classification of Diseases codes were used to determine melanoma outcome.

Results: After adjusting for potential confounders, participants in the highest category of total citrus intake (> 2 servings per day) had a significantly increased risk of melanoma (OR 1·63, 95% CI 1·24–2·12) relative to those with no consumption. For individual citrus products, participants with the most orange and orange juice consumption (> 1 serving per day) had a significantly increased melanoma risk relative to those with no consumption (OR 1·79, 95% CI 1·07–2·78 and OR 1·54, 95% CI 1·10–2·10, respectively). Fair- or very fair-skinned participants with high citrus consumption had an even greater melanoma risk (OR 1·75, 95% CI 1·31–2·29).

Conclusions: High citrus consumption was associated with an increased risk of melanoma in a large, prospective, population-based cohort. Further validation of these findings could lead to improved melanoma prevention strategies.

Introduction

Over the last several decades, there has been a dramatic increase in melanoma incidence worldwide.[1] In the UK, melanoma incidence has been increasing by an average of 3% per year since the 1980s,[2] and it is currently the fifth most common cancer diagnosis among UK residents.[3] Globally, melanoma incidence is increasing by 3–7% per year,[4] a rate faster than that of any other cancer,[1,4] suggesting a doubling in incidence every 10–20 years.[5] This increasing incidence is not artifactual,[6] and it is predicted to continue.[2,7,8] Melanoma is also the second most diagnosed cancer among young adults,[9] thus having the highest individual cost of cancer death regarding years of productive life lost.[10] Because of this rapid increase in melanoma rates, primary prevention research is necessary and urgent.

Several melanoma risk factors have been established, including exposure to ultraviolet (UV) radiation from the sun;[11,12] having fair skin, fair hair, light-coloured eyes or the inability to tan;[12–17] the use of solariums or sunlamps;[18,19] and a history of sunburn during adolescence.[17,20] Psoralen, a type of furocoumarin used in photochemotherapy using oral psoralen and UVA radiation, is also known to be photocarcinogenic.[21] Naturally occurring in nature as part of a plant's natural defence against pathogens,[22] psoralens are abundantly found in citrus products,[22–24] leading to the hypothesis that citrus consumption may increase melanoma risk due to psoralen photocarcinogenicity.

This fairly new hypothesis has yielded inconsistent results. Research from the Nurses' Health Study (NHS) and Health Professionals Follow-up Study (HPFS) found that high total citrus consumption was significantly associated with an increased risk of melanoma,[25] and research from the European Prospective Investigation into Cancer and Nutrition cohort (EPIC) found that high citrus fruit consumption (but not total citrus consumption) increased melanoma risk.[26] Conversely, an analysis of the Women's Health Initiative (WHI) found no association between citrus consumption and melanoma risk, except among those with the highest consumption of citrus juice and the most time spent outdoors.[27] Findings from the National Institutes of Health and the AARP (NIH-AARP) were also null.[28] The only other research to investigate this association is an Italian case–control study of the Mediterranean diet, which found high citrus consumption to be a protective factor.[13] This sparse, conflicting evidence represents a critical gap in melanoma knowledge and highlights the need for further investigation of citrus as a potential melanoma risk factor.

The purpose of the current study was to address these gaps in knowledge by performing the following analyses in the UK Biobank (UKBB), a large, population-based, prospective cohort: (i) to investigate the association between total citrus consumption and melanoma risk, (ii) to investigate the association between individual citrus products and melanoma risk, and (iii) to test for interactions between total citrus intake and established melanoma risk factors. We believe the results of the current study will increase current knowledge and understanding of skin cancer risk factors, and, upon further validation, can serve as an empirical basis for future primary prevention interventions.

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