Association of Citrus Consumption with Risk of Incident Malignant Melanoma: Results from Two Prospective Cohort Studies

Abstract

Background: Citrus products are dietary sources of psoralens, a group of naturally occurring furocoumarins that have photocarcinogenic properties. The association between citrus consumption and risk of malignant melanoma remains unclear. Objective: We examined the association between citrus consumption and risk of subsequent malignant melanoma among 63,810 women in the Nurses' Health Study (1984-2010) and 41,622 men in the Health Professionals Follow-up Study (1986-2010). Methods: Dietary intake was repeatedly assessed using a validated food frequency questionnaire every 2 to 4 years during the follow-up. Incident melanoma cases were reported biennially and confirmed by medical and pathological reports. Cox proportional hazards models were used to estimate the hazard ratios (HR) with 95% confidence intervals (CI) of melanoma associated with dietary consumption. Results: We documented 1,857 incident melanomas over 2 million person-years of follow-up. Compared to participants who consumed citrus products less than twice per week, the pooled multivariate HRs for melanoma were 1.10 (95% CI, 0.93-1.30) for those who consumed twice to four times per week, 1.25 (95% CI, 1.07-1.46) for five to six times per week, 1.25 (95% CI, 1.07-1.46) for once to 1.5 times per day, and 1.36 (95% CI, 1.14-1.63) for 1.6 or more times per day (P<0.001 for trend). Among the individual citrus products, grapefruit showed the most consistent positive association with risk of melanoma, followed by orange juice. The pooled multivariate hazard ratios for melanoma were 1.44 (95% CI, 1.11-1.87) comparing the extreme consumption categories of grapefruit (three times or more per week vs. never, P=0.002 for trend) and 1.26 (95% CI, 1.02-1.56) comparing the extreme consumption categories of orange juice (once or more per day vs. never, P=0.001 for trend). Conclusion: In two large prospective cohorts of health professionals, citrus consumption was associated with an increased risk of malignant melanoma.