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Unformatted text preview: .edu Received February 13,
2003; accepted for publication August 27, 2003. ©AlphaMed Press 1083-7159/2003/$12.00/0 The Oncologist 2004;9:182-187 www.TheOncologist.com 183 have been experienced with interleukin-2 therapy. In light of
the rising incidence and high mortality rate in advanced disease, several countries now recognize melanoma as a top
public health priority. This article reviews selected recent
advances in the understanding of melanoma biology that
involve the initiation, progression, and programmed cell
UV LIGHT AND MELANOMA
UV light has been implicated in the genesis of several
forms of cutaneous malignancies: squamous cell carcinoma,
basal cell carcinoma, and melanoma. Epidemiological studies
reveal a strong association between melanoma formation and
sunlight exposure. Whereas squamous and basal cell carcinomas appear to be linked to total lifetime sun exposure,
melanoma development is most closely associated with
intense, intermittent exposure [5-9]. A history of sunburn is
often used as a surrogate measure for intense intermittent
exposure. The odds ratios for increased risk of melanoma due
to sunburns in adult life, adolescence, and in childhood were
1.91, 1.73, and 1.95, respectively. In addition, the locations of
melanomas suggest causation by intermittent sun exposure.
Melanomas occur relatively less frequently in areas that are
continuously exposed to sunlight, like the face, hands, and
arms, and more frequently in sun-protected areas receiving
intermittent exposure, like the trunk in men and the backs of
legs in women .
Experimental studies support the epidemiologic evidence implicating sun exposure in causing melanoma.
Intense intermittent exposure apparently does not give
melanocytes time to synthesize melanin to protect themselves from UV irradiation. This irradiation leads to DNA
mutations. Although UV-A light is more abundant in sunlight than UV-B light, the latter is responsible for several
types of DNA lesions; it induces cyclobutane-pyrimidine
dimers and pyrimidine-pyrimidone photoproducts [10-11].
DNA mutations result from incorrect repair of these lesions
. Prolonged sun exposure allows melanocytes to increase
melanin production. UV-B light can stimulate the transfer of
melanin to form protective caps above the nuclei of
suprabasal keratinocytes. During intense intermittent exposure, however, cells receive large doses of UV radiation
without protection from increased melanin synthesis. In addition, melanocytes contain several prosurvival or antiapoptotic proteins. These may inhibit cell death following intense
UV exposure [12-14]. Therefore, melanocytes can receive
intense mutagenic UV light and survive. If they are stimulated by growth factors, chances for transformation increase
. UV-B irradiation may also stimulate melanoma genesis
by modulating growth factors, inhibiting the endogenous
antioxidant system, or inhibiting cell-mediated immunity. Recent Advances in Melanoma Biology
Animal experimental systems support a role for UV light
in melanoma causation. For ex...
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