PerspectiveIn the Journals

Citrus consumption may increase malignant melanoma risk

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July 23, 2015

The consumption of citrus fruits corresponded with an increased risk for malignant melanoma in two independent cohorts, according to study results.

Citrus products contain psoralens and furocoumarins, both naturally occurring chemicals with potential photocarcinogenic properties, according to study background.

“Whether dietary consumption of psoralen-rich foods may increase melanoma risk is unknown, and whether the public should be advised about dietary psoralens remains a question,” Abrar A. Qureshi, MD, MPH, chief of dermatology at Rhode Island Hospital and chair of dermatology at the Warren Alpert Medical School at Brown University, and colleagues wrote.

Qureshi and colleagues evaluated data from two independent studies: the Nurses’ Health Study (n = 63,810; 100% women), conducted between 1984 and 2010; and the Health Professionals Follow-Up Study (n = 41,622; 100% men), conducted between 1986 and 2010.

During follow-up, the researchers assessed dietary information every 2 to 4 years. Patients self-reported incident melanoma diagnoses, which the researchers confirmed through pathologic records.

Overall, 1,840 incident melanoma diagnoses occurred in the population.

After adjusting for other risk factors such as family history of melanoma and sunburn susceptibility as a child or adolescent, researchers observed an increased risk for incident melanoma associated with citrus consumption 2 to 4 times per week (HR = 1.1; 95% CI, 0.94-1.3), 5 to 6 times per week (HR = 1.26; 95% CI, 1.08-1.47), 1 to 1.5 times per day (HR = 1.27; 95% CI, 1.09-1.49) and more than 1.6 times per day (HR = 1.36; 95% CI, 1.14-1.63) compared with consumption less than twice per week.

Grapefruit exhibited the strongest association with melanoma risk, independent of other lifestyle or dietary factors. Consumption of a large amount of grapefruit (≥ 3 times per week) increased the risk for melanoma compared with never consuming grapefruit (HR = 1.41; 95% CI, 1.1-1.82).

Further, orange juice consumption once or more daily also significantly increased the risk for melanoma (HR = 1.25; 95% CI, 1.07-1.47).

The researchers acknowledged the inclusion of only U.S. health professionals in their study population as a limitation of their study.

“These findings provide evidence for the potential photocarcinogenic effect of psoralen-rich foods,” Qureshi and colleagues concluded. “Although our findings are consistent with evidence from animal experiments, which revealed a potential synergistic effect between psoralens and UV radiation, further investigation is needed to confirm our findings and guide sun exposure behaviors among individuals with high citrus consumption.”

Marianne Berwick, PhD, MPH

Marianne Berwick

Although the study findings may hold value, they should be confirmed in further studies before these data inform dietary advice for melanoma, Marianne Berwick, PhD, MPH, distinguished professor of internal medicine and dermatology at the University of New Mexico, wrote in an accompanying editorial.

“This is a potentially important study, given that citrus consumption is widely promulgated as an important dietary constituent and has demonstrated benefit for coronary heart disease, cancer prevention and overall health effects,” Berwick wrote. “At this point in time, a public overreaction leading to avoidance of citrus products is to be avoided. … There is clearly a need for replication of the study findings in a different population before modifying current dietary advice to the public.” – by Cameron Kelsall

Disclosure: Qureshi reports research funding from Regeneron, advisory roles with AbbVie, Janssen Pharmaceuticals, Novartis and Pfizer, and employment and leadership roles with University Dermatology. The other researchers and Berwick report no relevant financial disclosures.

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Laura McGirt

Laura McGirt

It has long been known that natural plant products — psoralens — are associated with increased photosensitivity in humans. Indeed, we use these agents to further sensitize patients undergoing photochemotherapy (ultraviolet light plus psoralen), which is used to treat a variety of skin diseases. Ultraviolet exposure itself is associated with risk for melanoma, and patients undergoing photochemotherapy also have an increased risk for skin cancer, including melanoma. It was hypothesized that dietary psoralen intake, including citrus fruits that have robust psoralen content, may also be associated with melanoma.
A study by Wu and colleagues published in Journal of Clinical Oncology demonstrates that those with higher levels of orange juice and grapefruit intake had an increased risk for melanoma. Using data from over 100,000 men and women in the Nurses’ Health Study and Health Professionals Follow-Up Study, the authors demonstrated that after adjusting for known risk factors and potential confounders, subjects who consumed citrus more than 1.6 times a day had a 36% increased risk for melanoma vs. those who consumed citrus less than two times a week.
Specifically, when grapefruit — known to have higher levels of psoralens — was consumed more than three times per week, there was a 41% increased risk for melanoma compared with not eating grapefruit. Orange juice consumption was associated with a 25% increased risk for melanoma in those who drank orange juice more than once daily vs. those who drank it less than once per week. Interestingly, grapefruit juice and orange consumption were not associated with increased risk for melanoma, and the researchers note that the overall reduced intake of these may have led to the results.
The researchers also are quick to note that, despite their findings, fruit consumption also has been found to be beneficial in various other chronic diseases/malignancies, and they do not advocate for reduced citrus intake.
Although further studies will be required to truly understand the risk for melanoma associated with citrus intake, the data certainly are compelling to alert patients with high citrus intake of their potential increased melanoma risk and further encourage them to practice sun-protective measures.

Laura McGirt, MD
Levine Cancer Institute
Carolinas HealthCare System

Disclosure: McGirt reports no relevant financial disclosures.