Melanoma etiology: where are we?

Abstract

Melanoma incidence rates are rising rapidly, particularly in older men. Older men are also more likely to have thick melanomas, which confer high mortality and morbidity. The reasons for the rate of increase are not known; increasing sun and UV exposure, however, is the major hypothesized explanation. In the past several years, two major susceptibility genes for melanoma, CDKN2A and CDK4, have been identified, but the two genes together account for a minority of familial melanoma. Other highrisk susceptibility genes are being sought actively. Genetic epidemiologic studies suggest that penetrance of each of the two identified genes is altered by other factors, either genetic or environmental. Epidemiologic studies have also identified other major host factors important in the development of melanoma. In European, North American, and Australian populations, the presence of clinically identified dysplastic nevi confers greatly increased risk of melanoma. A new measure of sun exposure, based on individual residential history, confers substantially increased risk of melanoma. Recent surveys of sun behavior in the US reveal extensive sunburning and use of tanning beds in adolescents and adults. Sun protective behaviors are not as prevalent as in Australia, where population rates of melanoma are stabilizing.

Melanoma Epidemiology and Prevention

“…Nevi A major risk factor for melanoma is number and type of nevi. Nevi are benign collections of melanocytes, and the numbers of nevi have been implicated in numerous studies as the most important risk factor for melanoma, with an increased number of nevi associated with an increased risk of disease [15,24,158,230]. A meta-analysis has shown that individuals with more than 100 normal nevi are at an almost seven times greater risk than individuals with few (≤15) nevi [75,76].…”

“…An inverse relationship has been consistently demonstrated between melanoma risk and degree of skin pigmentation [6,24,159]. Fair-skinned individuals have a much higher risk for developing melanoma than dark-skinned individuals, such that risk estimates in individuals of non-European descent, who are typically darker-skinned, are up to 10-20-fold less than those in individuals of European descent, who are typically lighter-skinned [15,230].…”

“…Skin that freckles easily has a tendency to burn or an inability to tan, showing an increased propensity for the disease [37, 159,230]. Some authors have hypothesized that skin reaction contributes less to melanoma risk than actual skin color, while others have postulated that skin reaction is a better predictor of risk than skin color [6,159].…”

Genomic profiling of malignant melanoma using tiling-resolution arrayCGH

“…Cutaneous malignant melanoma (CMM) is an aggressive form of skin cancer with increasing incidence in the Western world (Tucker and Goldstein, 2003). CMM has a heterogeneous and unpredictable clinical course with a potential for aggressive growth and refractoriness to available chemotherapy.…”

FGFR4 Arg388 allele correlates with tumour thickness and FGFR4 protein expression with survival of melanoma patients

“…The rising incidence makes this cancer an issue of ever increasing clinical and economic importance and research interest (Garland et al, 2003;Tucker and Goldstein, 2003;Berwick et al, 2005). The identification of new prognostic markers may help to better distinguish low from high-risk disease apart from the classical histopathologic and clinical criteria (Carlson et al, 2005) and may offer new targets for therapy.…”