Clinical Review
Ultraviolet A and melanoma: A review,☆☆,

https://doi.org/10.1067/mjd.2001.114594Get rights and content

Abstract

The incidence and mortality rates of melanoma have risen for many decades in the United States. Increased exposure to ultraviolet (UV) radiation is generally considered to be responsible. Sunburns, a measure of excess sun exposure, have been identified as a risk factor for the development of melanoma. Because sunburns are primarily due to UVB (280-320 nm) radiation, UVB has been implicated as a potential contributing factor to the pathogenesis of melanoma. The adverse role of UVA (320-400 nm) in this regard is less well studied, and currently there is a great deal of controversy regarding the relationship between UVA exposure and the development of melanoma. This article reviews evidence in the English-language literature that surrounds the controversy concerning a possible role for UVA in the origin of melanoma. Our search found that UVA causes DNA damage via photosensitized reactions that result in the production of oxygen radical species. UVA can induce mutations in various cultured cell lines. Furthermore, in two animal models, the hybrid Xiphophorus fish and the opossum (Mondelphis domestica), melanomas and melanoma precursors can be induced with UVA. UVA radiation has been reported to produce immunosuppression in laboratory animals and in humans. Some epidemiologic studies have reported an increase in melanomas in users of sunbeds and sunscreens and in patients exposed to psoralen and UVA (PUVA) therapy. There is basic scientific evidence of the harmful effects of UVA on DNA, cells and animals. Collectively, these data suggest a potential role for UVA in the pathogenesis of melanoma. To date evidence from epidemiologic studies and clinical observations are inconclusive but seem to be consistent with this hypothesis. Additional research on the possible role of UVA in the pathogenesis of melanoma is required. (J Am Acad Dermatol 2001;44:837-46.)

Section snippets

Basic science evidence

Cancer may be viewed as a disease that progresses through multiple stages that involve initiation, promotion, progression, and metastasis. Each stage is accompanied by further changes in DNA. UVB is known to cause mutations in oncogenes and tumor suppressor genes that eventually initiate the cascade of events resulting in skin cancers.14, 15, 16 To substantiate that UVA has the potential to induce melanoma, it is necessary to demonstrate that UVA is capable of producing biologic damage. It has

Epidemiologic evidence

Epidemiologic observations often reveal associations that provide valuable clues and new channels for further investigations, but these observations are not a substitute for understanding the pathogeneses of diseases. The validity of epidemiologic studies can be undermined by recall bias and confounding factors.

Clinical evidence

There are few controlled clinical studies investigating the independent effects that UVA radiation exerts on human skin. However, there are several clinical situations in which UVA is used to treat cutaneous diseases (eg, psoriasis, atopic dermatitis, cutaneous T-cell lymphomas, granuloma annulare, scleroderma)89 from which indirect conclusions can be drawn. Unlike therapeutic UVB radiation, therapeutic UVA plus psoralens is associated with the development of large, irregular, unevenly

Discussion

In this review, we have examined evidence from various disciplines that surround the controversy concerning UVA as a causative factor in the development of human melanoma. Although no studies have shown this conclusively, we believe that the evidence currently available to us does not allow this relationship to be ruled out.

The clinical implications of a role for UVA in causing human melanoma are important. People who frequently use sunbeds and sunlamps have exposed themselves to large

Acknowledgements

We thank Darrell S. Rigel, MD, for his valuable suggestions. Brookhaven National Laboratory is operated by Brookhaven Science Associates for the US Department of Energy. We thank Jackie M. Tripp, MD, for his assistance in the preparation of this manuscript.

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    Supported by The Ronald O. Perelman Department of Dermatology, New York University School of Medicine; Joseph H. Hazen Foundation; Mary and Emanuel Rosenthal Foundation; Kaplan Comprehensive Cancer Center (Cancer Center Support Core Grant 5P30-CA-16087); the Blair O. Rogers Medical Research Fund; Rahr Family Foundation; and Stavros S. Niarchos Foundation fund of the Skin Cancer Foundation.

    ☆☆

    Reprint requests: Alfred W. Kopf, MD, The Ronald O. Perelman Department of Dermatology, New York University School of Medicine, 550 First Ave, H164, New York, NY 10016. E-mail: [email protected].

    J Am Acad Dermatol 2001;44:837-46

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