Citrus Consumption and Risk of Cutaneous Malignant Melanoma

Abstract

Purpose: Citrus products are widely consumed foods that are rich in psoralens and furocoumarins, a group of naturally occurring chemicals with potential photocarcinogenic properties. We prospectively evaluated the risk of cutaneous malignant melanoma associated with citrus consumption.

Methods: A total of 63,810 women in the Nurses' Health Study (1984 to 2010) and 41,622 men in the Health Professionals Follow-Up Study (1986 to 2010) were included. Dietary information was repeatedly assessed every 2 to 4 years during follow-up. Incident melanoma cases were identified through self-report and confirmed by pathologic records.

Results: Over 24 to 26 years of follow-up, we documented 1,840 incident melanomas. After adjustment for other risk factors, the pooled multivariable hazard ratios for melanoma were 1.00 for overall citrus consumption < twice per week (reference), 1.10 (95% CI, 0.94 to 1.30) for two to four times per week, 1.26 (95% CI, 1.08 to 1.47) for five to six times per week, 1.27 (95% CI, 1.09 to 1.49) for once to 1.5 times per day, and 1.36 (95% CI, 1.14 to 1.63) for ≥ 1.6 times per day (Ptrend < .001). Among individual citrus products, grapefruit showed the most apparent association with risk of melanoma, which was independent of other lifestyle and dietary factors. The pooled multivariable hazard ratio for melanoma comparing the extreme consumption categories of grapefruit (≥ three times per week v never) was 1.41 (95% CI, 1.10 to 1.82; Ptrend < .001).

Conclusion: Citrus consumption was associated with an increased risk of malignant melanoma in two cohorts of women and men. Nevertheless, further investigation is needed to confirm our findings and explore related health implications.

Fig 1.

Hazard ratios (HRs) for incident melanomas comparing extreme citrus consumption categories at lags from 0 to 14 years. HRs were computed for overall citrus consumption comparing ≥ once per day versus < twice per week, for grapefruit and grapefruit juice consumption comparing ≥ twice per week versus never, for orange consumption comparing ≥ three times per week versus never, and for orange juice consumption comparing ≥ five times per week versus < once per week. In lagged analyses, we added different intervals from 2 to 14 years between dietary assessment and cohort follow-up (eg, we used citrus consumption from 1984 questionnaire for follow-up from 1986 to 1988 for 2-year lag analysis and for follow-up from 1988 to 1990 for 4-year lag analysis). Multivariable HRs were adjusted for age, family history of melanoma, natural hair color, No. of arm moles, sunburn susceptibility as child or adolescent, No. of lifetime blistering sunburns, cumulative ultraviolet flux since baseline, average time spent in direct sunlight since high school, body mass index, physical activity, smoking status, and intake of total energy, alcohol, coffee, and vitamin C from supplements. Analyses for consumption of each individual citrus product were also adjusted for consumption of other individual citrus products. Analyses for women were also adjusted for menopausal status and postmenopausal hormone use (Table 2). Results among women and men were pooled using random-effects model. HRs for other categories of citrus consumption in lagged analyses are shown in Data Supplement. Vertical lines represent 95% CIs; x-axis indicates years of lag.