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.

Epidemiological Assessments of Skin Outcomes in the Nurses’ Health Studies

“…For example, PGC-1β polymorphisms have been associated with tanning ability and melanoma susceptibility, which along with basic science data supported the regulatory role of PGC-1 coactivators in human tanning. 45 Following our epidemiologic findings on citrus consumption and melanoma, 37 further research into furocoumarin levels in citrus fruit and juice and participants' blood samples is in progress to confirm the photocarcinogenesis hypothesis.…”

“…37 The association appeared strongest for grapefruit. Consistent with a potential synergistic effect between psoralens and UV radiation, the association appeared to be stronger among those with a higher susceptibility to sunburn as a child or adolescent, those with more blistering sunburns, and those who spent more time in direct sunlight.…”

History of Keratinocyte Carcinoma and Risk of Melanoma: A Prospective Cohort Study

“…Epidemiologic studies in recent years have reported that associations between skin cancer risk and a number of other environmental factors besides sun exposure either may have protective (eg, caffeine) or potentiate (eg, citrus products) effects on the incidence of skin cancer (14)(15)(16)(17). However, little is known about whether these potential skin cancer risk factors may modify the relationship between KC history and melanoma.…”

“…Information on dietary factors, including consumption of citrus products, alcohol, and coffee, was repeatedly collected using a validated food frequency questionnaire at least every four years during the follow-up (17). Data on the following phenotypic and sun exposure-related factors were also collected in the follow-up questionnaires: ethnicities; family history of melanoma in first-degree relatives (parents, siblings, or offspring); natural hair color at an early age (age 21 years in NHS, and age 18 years in NHSII/HPFS); number of moles on extremity (arms in NHS/HPFS and legs in NHSII); skin reaction after prolonged sun exposure as a child/adolescent; number of severe or blistering sunburns; average time spent in direct sunlight in summer months since high school; regular use of sunscreen in summer months; and cumulative UV flux since baseline (a measure of long-term UV exposure) (14,17,21).…”

Citrus and melanoma risk: better to consume with dinner?

“…PUVA therapy (oral Psoralen with UVA light radiation), is a very effective treatment for psoriasis, but in rare instances it can contribute to the development of melanoma . Psoralen is a furanocoumarin and sensitizes the skin to UV light exposure . Citrus fruits are high in Vitamin C, which is necessary for collagen synthesis and wound healing, and have been shown to have other benefits including neuroprotection, improvement in lipid profiles and inflammatory markers, reduction of cardiovascular risk, and serve as a rich source of antioxidants .…”