Published in the Journal of Clinical Oncology, the study found people who consumed high amounts of whole grapefruit or orange juice were over a third more likely to develop melanoma, compared with those who consumed low amounts.
However, lead study author Dr. Shaowei Wu, of the Department of Dermatology at the Warren Alpert Medical School of Brown University in Providence, RI, and colleagues stress that further research is needed before any changes are made to recommendations for orange and grapefruit consumption.
According to the American Cancer Society, 73,870 people in the US will be diagnosed with melanoma this year and 9,940 people will die from the cancer.
The primary risk factor for melanoma is exposure to ultraviolet (UV) radiation from the sun and indoor tanning devices, such as tanning beds and sun lamps.
Past research has suggested that tanning lotions containing psoralens - a group of naturally occurring substances called furocoumarins that are found in citrus fruits - may increase the risk of melanoma by sensitizing the skin to the effects of UV radiation.
For their study, Dr. Wu and colleagues set out to see whether consumption of citrus fruits may be associated with greater risk of melanoma.
The team analyzed data from 63,810 women who were part of the Nurses' Health Study between 1984 and 2010, as well as 41,622 men who were part of the Health Professionals Follow-Up Study between 1986 and 2010.
All participants completed dietary questionnaires at least every 4 years, from which the researchers were able to gather information on their citrus fruit intake. In the study, a serving of citrus fruit was defined as the equivalent to one orange, half a grapefruit or one 6 oz glass of whole orange or grapefruit juice.
The participants also completed health questionnaires every 2 years, which detailed lifestyle factors - such as smoking status and physical activity levels - and medical history. Subjects with a history of cancer were excluded from analysis.
Consuming citrus fruits more than 1.6 times daily linked to 36% higher melanoma risk
During the 24-26-year follow-up, 1,840 participants were diagnosed with melanoma.
The researchers found that the more servings of oranges, grapefruits or juices from these fruits that the participants consumed overall, the higher their risk of melanoma. Subjects who consumed a serving of these fruits or their juices at least 1.6 times a day, for example, were found to be at 36% higher melanoma risk.
On analyzing melanoma risk by consumption of individual citrus products, the researchers found that grapefruit juice and whole oranges were not independently associated with greater risk of the cancer.
Fast facts about melanoma
- In the US, rates of melanoma have been increasing for the past 30 years
- The average age at melanoma diagnosis is 62, though it is still common among younger adults
- White Americans are around 20 times more likely to develop melanoma than African-Americans.
Eating whole grapefruit, however, was strongly associated with high melanoma risk, and this risk was found to be independent of confounding factors, such as age, smoking status, alcohol and coffee intake, use ofvitamin C supplements and physical activity levels.
Individuals more susceptible to sunburn as a child or teenager and those who had higher exposure to direct sunlight were at highest risk of melanoma from whole grapefruit consumption, the researchers found.
Orange juice was also associated with greater melanoma risk, which the researchers say is most likely because consumption of this product was much higher than consumption of other citrus products.
Though Dr. Wu and colleagues did not investigate the mechanisms underlying the association between citrus fruit consumption and melanoma risk, they speculate that it may be because the fruits are rich in psoralens and furocoumarins, which are believed to make the skin more sensitive to the sun.
"These substances are potential carcinogens, as found in both mice and humans. Psoralens and furocoumarins interact with UV light to stimulate melanoma cells to proliferate," explains Dr. Marianne Berwick, of the University of New Mexico in Albuquerque, in an editorial linked to the study.
However, the team notes no association was found between consumption of other foods rich in furocoumarins - such as celery and carrots - and increased risk of melanoma. But Dr. Wu says this is likely because people often cook these vegetables, and the heat reduces furocoumarin levels.
A 'public overreaction' to these findings should be avoided
According to Dr. Gary Scwartz, expert at the American Society of Clinical Oncology (ASCO), the findings from Dr. Wu and colleagues are "intriguing," though he says it is far too soon to make any changes to recommendations regarding citrus fruit consumption.
Dr. Wu adds:
"While our findings suggest that people who consume large amounts of whole grapefruit or orange juice may be at increased risk for melanoma, we need much more research before any concrete recommendations can be made.At this time, we don't advise that people cut back on citrus - but those who consume a lot of grapefruit and/or orange juice should be particularly careful to avoid prolonged sun exposure."
Dr. Berwick says this is a "potentially important" study, noting that citrus consumption is widely promoted for its health benefits. For example, past research has suggested grapefruit can aid weight loss and improve heart health.
However, she notes that at present, a "public overreaction" that may cause people to shun citrus fruits should be avoided.
"For people who would be considered at high risk, the best course might be to advise individuals to use multiple sources of fruit and juice in the diet and to use sun protection, particularly if one is sun sensitive," she adds. "There is clearly a need for replication of the study findings in a different population before modifying current dietary advice to the public."
Dr. Wu and colleagues plan to conduct a study that involves measuring furocoumarin levels in blood samples of subjects who consume high levels of citrus fruits, in order to determine whether it is these substances that may drive greater melanoma risk.
