Relationship between Dietary Furocoumarins and Melanoma Risk

Furocoumarins are a class of photocarcinogenic and phototoxic compounds found naturally in numerous edible plants. Experimental evidence shows that when combined with UV radiation, furocoumarins may become photoactivated and induce DNA crosslinks, leading to DNA damage and carcinogenesis. Therefore, a link between dietary furocoumarins and melanoma has been proposed. This project aims to examine the relationship between dietary furocoumarins and melanoma risk through three specific aims. First, we examined the kinetics of dietary furocoumarins in healthy adults (Aim 1). As early as 15 minutes after consuming grapefruit, and for up to three or more hours after ingestion, furocoumarins were detectable in plasma. This suggests that furocoumarins may be rapidly absorbed from dietary sources and the exposure period may last multiple hours. Secondly, we examined the furocoumarin contents of popular foods and estimated exposure among US adults (Aim 2). We measured the concentrations of seven major furocoumarins in 29 foods and linked the resulting database to dietary data from the National Health and Nutrition Examination Survey (NHANES) 2003-2012. Furocoumarins were consumed by the large majority of adults, and average daily intake among US adults was 81.4 µg/day. Finally, we conducted multiple epidemiologic studies to investigate the relationship between furocoumarin intake and melanoma risk (Aim 3). Using NHANES 2003-2012 data, we observed a linear trend toward higher odds of melanoma history among those with the highest furocoumarin intakes, but this relationship was not statistically significant. In a prospective study of participants of the Women’s Health Initiative, citrus juice intake was associated with increased melanoma risk among women who spent the most time outdoors in summer as adults, but no significant associations were observed with whole citrus fruits or among other subgroups of women. In the NIH-AARP Diet and Health Study, those with the highest furocoumarin intake from citrus had significantly increased risk of melanoma compared to the lowest quintile, but there was no significant trend in risk across intake levels. These findings suggest that dietary furocoumarins may be associated with melanoma risk among certain vulnerable subgroups, but future work is needed to clarify these findings and examine possible mechanisms underlying this relationship