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Citrus consumption linked to risk of cutaneous malignant melanoma

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These findings require replication

This study does not fulfill all of Hill’s criteria [of causation] and cannot be considered definitive. The strength of association is relatively small, with a hazard ratio (HR) of 1.36 for the highest consumption of citrus and HR of 1.41 for the highest consumption of grapefruit. Conversely, dietary effects on disease incidence are rarely large.

There is no other study in another population that has found this relationship between grapefruit or citrus consumption and the development of melanoma, and thus, there is little consistency in these findings. It should be noted that a much smaller case-control study of melanoma in Italy found a protective effect for dietary vitamin C on melanoma incidence (HR, 0.59) and another small case-control study of melanoma in Hawaii found no significant association between dietary vitamin C and the development of melanoma.

A number of factors limit enthusiasm for this study. The first and most important factor is that the study population is not representative of the general population.

For instance, in support of the differences between the study population and the general population, in two population-based studies we conducted – one in the state of Connecticut and the other an international study in four countries – mean Breslow thickness, the major prognostic factor for melanoma, was 1.49 mm and 1.28 mm, respectively, whereas in this study, the mean Breslow thickness was 0.63 mm. Such a large difference could be accounted for by the fact that these were health professionals who developed melanoma and might be expected to pay more attention to unusual lesions. Such differences underline the lack of representativeness of the population studied.

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. At this point in time, a public overreaction leading to avoidance of citrus products is to be avoided. For people who would be considered at high risk, the best course might be to use multiple sources of fruit and juice in the diet and to use sun protection, particularly if one is sun sensitive. There is clearly a need for replication of the study findings in a different population before modifying current dietary advice to the public.

Marianne Berwick, Ph.D., is with the department of internal medicine at the University of New Mexico, Albuquerque. Dr. Berwick is supported by grants from the National Institutes of Health and the National Cancer Institute. Dr. Berwick’s comments were taken from an editorial response (J. Clin. Oncol. 2015 June 29 [doi:10.1200/JCO.2015.61.8116]).


 

FROM THE JOURNAL OF CLINICAL ONCOLOGY

References

Health professionals from two cohort studies who consumed citrus products more than 1.6 times a day had a 36% higher risk of developing cutaneous malignant melanoma, compared with those who consumed citrus less than twice a week, a large prospective study showed.

Among citrus products studied, consumption of whole grapefruit, but not grapefruit juice, showed the most apparent association with melanoma risk, Shaowei Wu, Ph.D., of Brigham and Women’s Hospital, Boston, and associates reported online June 29 (J. Clin. Oncol. 2015 [doi:10.1200/JCO.2014.57.4111]).

“These findings provide evidence for the potential photocarcinogenic effect of psoralen-rich foods,” the researchers wrote. “However, previous studies have also suggested that fruit intake may have potential beneficial effects for the prevention of chronic diseases, such as breast cancer and type 2 diabetes. 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.”

©Ls9907/Thinkstockphotos.com

For the analysis, the researchers evaluated dietary information from 63,810 women in the Nurses’ Health Study (1984-2010) and 41,622 men in the Health Professionals Follow-up Study (1986-2010). In these studies, dietary information was assessed every 2-4 years during follow-up, while incident melanoma cases were identified through self-report and confirmed by pathology.

During a follow-up period of 24-26 years, the researchers documented 1,840 incident melanomas. After adjusting for risk factors, the pooled multivariable hazard ratios for melanoma were 1.00 for overall citrus consumption less than twice per week (reference), 1.10 for two to four times per week, 1.26 for five to six times per week, 1.27 for 1-1.5 times per day, and 1.36 for 1.6 times per day or more.

“Interestingly, fresh grapefruit showed the most apparent association with melanoma among individual citrus products, which may be explained by its higher levels of psoralens and furocoumarins when compared with oranges,” wrote the researchers, who found that the pooled multivariable HR for melanoma was 1.41 for the highest consumption of grapefruit (defined as three or more times per week, versus none).

“The significant but less apparent association between [consumption of] orange juice with melanoma risk may be partly explained by its much higher consumption levels, which contributed to greater than 50% of overall citrus consumption, whereas the null association of grapefruit juice with melanoma risk may be a result of its much lower consumption levels and a large number of nonconsumers, as compared with the other individual citrus products,” they said.

In addition, Dr. Wu and associates found that the association between grapefruit consumption and melanoma was more apparent among those with a history of sunburn and higher exposure to UV radiation. The association also appeared to be stronger “for melanomas on body sites with higher continuous sun exposure (e.g., head, neck, and extremities) than for melanomas on body sites with lower continuous sun exposure (e.g., truncal sites), which may suggest a potential synergistic effect between dietary consumption and solar UV radiation.”

They acknowledged certain limitations of the study, including the fact that the dietary data were self-reported and that the two cohorts were “mostly comprised [of] white, educated U.S. health professionals, which potentially limits the generalizability of the findings.”

Dr. Wu and five coauthors reported having no financial disclosures. A seventh coauthor, Dr. Abrar A. Qureshi, disclosed that he has a consulting or advisory role with Abbvie, Novartis, Janssen Pharmaceuticals, and Pfizer. He also has received research funding from Regeneron.

dbrunk@frontlinemedcom.com

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