Among individual citrus products, grapefruit showed the most apparent association with risk of melanoma, which was independent of other lifestyle and dietary factors.
—Marianne Berwick, PhD, MPH, and colleagues
A study finding a link between citrus consumption and increased risk of melanoma1 may provide food for thought about the findings and implications as well as whet the appetite for more evidence, but according to several experts commenting on the study, it does not mean you should stop eating citrus fruits.
“At this point in time, a public overreaction leading to avoidance of citrus products is to be avoided,” Marianne Berwick, PhD, MPH, wrote in an editorial accompanying the article in the Journal of Clinical Oncology.2 Yet in an interview with The ASCO Post, Dr. Berwick, Distinguished Professor, Department of Internal Medicine and Dermatology at the University of New Mexico, Albuquerque, said that was already happening. “Almost everywhere I go, I’ve had people asking about this,” she said, and whether they should stop eating citrus fruits. “It is a high-profile issue.”
That high profile can be attributed to the prevalence of citrus fruits in the diet and their previously acknowledged health benefits, as well as coverage of the study in the national media. That coverage quotes study authors and others cautioning against abandoning citrus fruits.
For example, in the NBC News coverage, study author Walter Willet, MD, of the Harvard School of Public Health, Boston, stated, “At this point in time, it is not a good idea to avoid citrus fruits.”3 In another article, the study’s corresponding author, Abrar A. Qureshi, MD, MPH, of the Warren Alpert Medical School at Brown University, Providence, Rhode Island, declared: “We are not recommending changing fruit consumption, as these fruits and vegetables are important for overall health.”4 These and other articles also cited Dr. Berwick’s editorial and noted, as she did, the importance of using sun protection to reduce the risk of melanoma.
Grapefruits and Orange Juice
Analyzing data on 63,810 women in the Nurses Health Study and 41,622 men in the Health Professionals, the study found a 36% higher risk of melanoma among those who consumed overall citrus items 1.6 times or more a day vs less than twice a week.
“Dietary intake was assessed using a validated food frequency questionnaire at least every 4 years,” according to the study report. “In all food frequency questionnaires, participants were asked how often on average (never to more than six servings per day) during the previous year they had consumed grapefruit (half), oranges (one), and grapefruit and orange juices (one small glass [6 oz]). Overall citrus consumption was calculated as the sum of these individual products.”
With up to 26 years of follow-up, 1,840 incident melanomas were documented. “Among individual citrus products, grapefruit showed the most apparent association with risk of melanoma, which was independent of other lifestyle and dietary factors,” the authors reported.
This apparent association between grapefruits and melanoma “may be explained by its higher levels of psoralens and furocoumarins when compared with oranges,” the researchers wrote in the study report. Psoralens and furocoumarins are “naturally occurring compounds with potential photocarcinogenic properties,” the researchers noted. “Psoralens had been used as tanning accelerators until 1996,” the investigators added, and individuals who had used psoralen tanning activators or sunscreens with psoralen had a higher risk of melanoma.
“Orange juice consumption also showed a significant but less apparent association with melanoma risk,” the researchers reported. This “may be partly explained by its much higher consumption levels, which contributed to more than 50% of overall citrus consumption,” the investigators stated. “Consumption of grapefruit juice and oranges was generally not associated with melanoma risk.”
The findings were independent of other lifestyle and dietary factors assessed. These factors included chronic diseases, family history of melanoma, exposure to sunlight, number of moles on arms, cigarette smoking, physical activity, vitamin C supplements, menopausal status, and postmenopausal hormone use among women. “Participants with higher citrus intake were less likely to smoke cigarettes and drink coffee, more likely to exercise, and had higher intake of individual citrus products and vitamin C,” the researchers reported. “In contrast, there was no appreciable difference in sun exposure–related variables and other host risk factors over the intake categories.”
Factors Limiting Study Enthusiasm
“The study has much strength. The rationale is clear, the study was large, and data were collected prospectively,” Dr. Berwick wrote in her editorial. She went on, however, to elucidate a “number of factors” that “limit enthusiasm for this study.”
“The first and most important factor is that the study population is not representative of the general population,” Dr. Berwick asserted. The mean Breslow thickness, “the major prognostic factor for melanoma,” was 0.63 mm, far lower than that in the general population studies, including two studies cited by Dr. Berwick, with mean Breslow thicknesses of 1.28 mm and 1.49 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,” she wrote.
Among the 1,840 documented cases of melanoma in the study, 891, or nearly 50%, were in situ melanomas. “These are very, very thin melanomas,” Dr. Berwick added in the interview with The ASCO Post, and “are often indolent. Very rarely do they cause problems.”
The study excluded people with a history of nonmelanoma skin cancer. “Such a history confers a twofold increased risk for developing melanoma. Thus, an artificial bias may have been introduced by eliminating a group who were at significant risk for developing melanoma and who might not have the same risk associated with citrus consumption,” Dr. Berwick pointed out.
“Why exclude them? That made no sense to me,” Dr. Berwick said. “You don’t know which direction that will bias the results. It might make them less significant, or it might make them more significant. We don’t know.”
Intermittent vs Continuous Sun Exposure
The study found “intermittent ultraviolet exposure, such as that obtained on weekends and holidays, was not associated with melanoma among this group. Instead, continuous exposure was associated, which is at odds with the current literature; continuous exposure does not demonstrate an increased risk for developing melanoma,” Dr. Berwick also noted.
In a previous article from the University of New Mexico, Dr. Berwick pointed out that the common lifestyle pattern of being indoors most of the week and then trying to make up for that by staying outdoors as much as possible during the weekend “puts us at higher risk for skin cancer because of our skin’s intermittent exposure to the sun. This irregular exposure prevents our skin from adapting to the sun’s damaging ultraviolet rays.”5
‘Clearly a Need for Replication’
“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,” Dr. Berwick concluded. In addition to warning against overreaction that could cause people to avoid eating citrus products, Dr. Berwick called for further epidemiologic studies. “There is clearly a need for replication of the study findings in a different population before modifying current dietary advice to the public,” she stated. ■
Disclosure: Dr. Berwick reported no potential conflicts of interest.
1. Wu S, Han J, Feskanich D, et al: Citrus consumption and risk of cutaneous malignant melanoma. J Clin Oncol. June 29, 2015 (early release online).
2. Berwick M: Dietary advice for melanoma: Not ready for prime time. J Clin Oncol. June 29, 2015 (early release online).
3. Fox M: Could too much citrus cause skin cancer? NBC News, June 29, 2015. Available at nbcnews.com. Accessed July 23, 2015.
4. Doyle K: Citrus fruit linked with melanoma in preliminary study. WHBL News, June 29, 2015. Available at whbl.com. Accessed July 23, 2015.
5. Frank L: Three questions for skin cancer investigator Dr. Marianne Berwick. University of New Mexico Health Sciences Center news release, May 1, 2014. Available at hscnews.unm.edu. Accessed July 23, 2015.