Could a Specific Dietary Intake Be a Risk Factor for Cutaneous Melanoma?

Vitamin A (retinol) is a fat-soluble, organic compound that cannot be synthesized by humans but is necessary for normal physiological function and therefore is classified as an essential nutrient. The main source of vitamin A in the human diet is from retinyl esters, mostly from animal products such as dairy products (eg, butter) as well as from plant-based, provitamin A carotenoids (α-carotene, β-carotene) that can be converted to retinol in the intestines.¹⁴

Some case-control studies have investigated the association of vitamin A intake and CM risk, reporting mixed findings. Naldi et al¹⁵ found a notable inverse association between vitamin A intake and CM risk. Le Marchand et al¹⁶ found no inverse association for carotenoids or retinol. Kirkpatrick et al¹⁷ found no evidence of a protective effect for vitamin A or carotenoids on CM. However, the Nurses’ Health Study and the Nurses’ Health Study II reported inverse associations between CM and retinol from foods and dietary supplements.⁸

Dairy products such as butter contain several components considered to be potentially anticarcinogenic, such as calcium, vitamin D, butyric acid, conjugated linoleic acid, sphingolipids, and probiotic bacteria. Some studies found an inverted association between melanoma and high intake of dairy products or other dietary sources of vitamin D, while some investigators showed no association.^6,18

Fortes et al¹⁸ assessed the role of diet on CM and found no protective effects of butter intake against the development of melanoma; however, a protective effect was found for carrots, which are rich in provitamin A (β-carotene) and for the regular intake of herbs rich in polyphenols (eg, rosemary). In our study, we found a protective effect against CM for butter but not for other dairy products. These findings could be explained by the high content of vitamin A in butter in comparison to other dairy products. Habitual intake of oregano also was associated with a protective effect for CM. Oregano is rich in polyphenols such as carvacrol, thymol, and rosmarinic acid, which are known for their antioxidant capacities and the inhibition of cyclooxygenase.^19-21 At experimental levels, both carvacrol and thymol have been shown to inhibit the growth of melanoma cells.^19,20 Rosmarinic acid, contained by both rosemary and oregano, have been shown at experimental levels to have photoprotective effects against melanoma.²¹

The relationship between dietary and nutritional intake and CM has a great potential that should be further explored. Tong and Young²² showed that proanthocyanidins found in grape seeds, epigallocatechin-3-gallate, resveratrol, rosmarinic acid, lycopene, and fig latex have demonstrated clear anticancer effects toward melanoma.

The strength of this study is the high response rate of both cases and controls and the use of incidence melanoma cases that decrease recall bias. A limitation of our study is that food portions were based on average portion size for each food item and therefore it can capture habitual consumption but not calculate actual nutrient intake. Misclassification of dietary exposure also could be a problem. Part of this misclassification is a result of a food frequency questionnaire being an imperfect measure of dietary history; however, we evaluated the reproducibility of the food frequency questionnaire used in this case-control study. Overall, there was a fair to good reproducibility between answers in 2 different periods (12 months apart). For example, agreement for frequency of intake of fresh herbs, tomatoes, and butter were 90.8%, 83.1%, and 83.3%, respectively.

Our sample size had sufficient statistical power to detect the effects of diet on CM.

Conclusion

Our study indicates that butter and oregano intake seem to have a protective role against the development of CM. Further studies are needed to confirm these findings.