Abstract

Simple SummaryCitrus products are rich in furocoumarins, which can increase the risk of incident non-melanoma skin cancer (NMSC) when combined with ultraviolet radiation. However, few observational studies have evaluated the link between citrus intake and NMSC incidence. The aim of this study was to determine whether citrus intake was related to the NMSC incidence in participants of the Women’s Health Initiative Observational Study. The results of this study indicated that high citrus juice consumption was associated with a higher risk of incident NMSC compared to low consumption. These findings add further evidence of the potentially carcinogenic nature of certain citrus products and highlight the need to continue investigations in identifying risk factors and mechanisms.Evidence from animal studies suggests that furocoumarins, compounds present in citrus products, can increase the risk of non-melanoma skin cancer (NMSC) when combined with ultraviolet radiation. The objective of this study was to determine the relationship between citrus intake and NMSC risk among postmenopausal women from the Women’s Health Initiative (WHI) Observational Study, who were aged 50–79 years at enrollment (1993–1998). The consumption of citrus fruit, citrus juice, and non-citrus fruit and juice were measured at the baseline of the study using a food frequency questionnaire (FFQ). NMSC cases (basal or squamous cell carcinomas) were self-reported during annual follow-up surveys. The outcome data used for this analysis were collected through March 2020. The relative risk (RR) for incident NMSC by citrus consumption was calculated. Among 49,007 non-Hispanic white participants, there were 8642 cases of incident NMSC. Using less than one serving of citrus juice per week as reference, the RRs and 95% confidence intervals (CI) for incident NMSC by citrus juice intake were 1.03 (0.95, 1.10) for one serving/week, 1.06 (1.00, 1.12) for two to four servings/week, 0.98 (0.90, 1.07) for five to six servings/week, and 1.08 (1.02, 1.13) for one or more serving/day (p-trend = 0.007). Subgroup analyses did not reveal meaningful associations by sun exposure variables. In conclusion, there were indications of a slightly higher risk of incident NMSC among citrus juice consumers; however, further longitudinal and mechanistic studies are needed to confirm the key risk factors.

Highlights

  • Non-melanoma skin cancer (NMSC), consisting primarily of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), is the most common cancer with increasing incidence rates [1,2] and predominately affects those with fair-skin [3]

  • Citrus juice consumption was moderately associated with the NMSC risk, but non-citrus fruit and juice, citrus fruit, and total citrus consumption were not associated with NMSC risk in models adjusting for sociodemographic variables, body mass index (BMI), physical activity, alcohol consumption, and sun-related variables

  • Citrus fruit was a risk factor for incident SCC, but not BCC, in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, while, in our study, the total citrus fruit consumption was not associated with the risk of NMSC

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Summary

Introduction

Non-melanoma skin cancer (NMSC), consisting primarily of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), is the most common cancer with increasing incidence rates [1,2] and predominately affects those with fair-skin [3]. There are several known risk factors for NMSC, including having a skin type that burns and/or tans poorly, fair complexion, increasing age, being male, and lifetime exposure to ultraviolet (UV) light [8]. Psoralen and ultraviolet A (PUVA) therapy, which uses orally or topically applied psoralen—a furocoumarin congener—in conjunction with UVA radiation to treat skin diseases, such as psoriasis, is well-known to increase the risk of skin cancer if used long term [13,15,16,17]

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