Current Perspective
Genetic epidemiology of melanoma

https://doi.org/10.1016/S0959-8049(03)00313-7Get rights and content

Abstract

Melanoma incidence has risen in many Caucasians populations over the last 20 years and research on the potential environmental and genetic risk factors has led to some interesting new findings but also to many more questions. The relationship between melanoma and ultraviolet radiation is complex and this area of research is controversial especially regarding the use of sunbeds and sunscreens. In terms of genetic factors, the discovery of two genes CDKN2A and CDK4 has been a great advance with more understanding of melanocyte biology in relation to defects in senescence. For phenotypic risk factors such as fair skin and high numbers of naevi, the role of genetic factors is clearly evident but these traits are complex and the discovery of genes involved in skin pigmentation and naevi formation is not an easy task. Research on the MC1R gene has not only shown the importance of this gene in hair and skin pigmentation but also in senescence and immunity. Functional studies involving CDKN2A and MC1R are leading to important new findings. There is also some hope regarding the use of micro-arrays in helping to dissect many genetic events in melanoma. The collection of large datasets including family, twin and case-control studies as well as tumour banks with collaborations between countries will hopefully lead to more discoveries. For the primary and secondary prevention of this tumour, efforts need to be sustained in public health campaigns on sun exposure and the recognition of individuals at high risk.

Section snippets

Changes in incidence

Melanoma although a relatively uncommon cancer has become an important public health issue because of rising incidence in Caucasian populations. It is estimated that over the last 50 years, the incidence has risen steadily by around 6% every year leading to a 10-fold increase in incidence since the late 1950s [1]. However, most recent figures have shown that in parts of the United States of America (USA), Canada, Australia and Europe, the incidence rates have reached a plateau or decreased [2].

Sun exposure

The association between melanoma and sun exposure although supported by latitude studies, migration studies and case-control studies is very complex. One of the obvious confounding factors in all studies looking at the effect of sun exposure is skin type. Although melanoma mainly affects fair-skinned individuals, it is still commonly found in subjects with skin types 3 and 4, who may tan very easily. The obvious difference in melanoma incidence between Australia (melanoma incidence in

Sunscreens and sunbeds

Sunscreens have long been promoted for skin cancer prevention, but their efficacy in reducing melanoma is unclear [9]. Moreover, recent studies have shown that the use of sunscreens can be associated with an increased risk of melanoma and this risk is likely to be explained by the suppression of sunburns which lead to longer exposure to UVR mainly within the UVA range [10]. Higher sun protection factor (SPF) sunscreens also increase mean cumulative sun exposure of young subjects in Europe and

Germline mutations

Melanoma like many other cancers has a genetic basis. It has long been observed that melanoma can cluster in some families. However, this is rare and the genes implicated in large melanoma families are likely to play a minor role in population-based melanomas. In melanoma genetics, the first germline (transmitted from one generation to the next) mutations in CDKN2A or p16 on chromosome 9p21 were discovered in large melanoma pedigrees in 1994 by the Utah group [22]. Mutations in CDK4, another

Conclusions

Melanoma is an important public health issue and research strategies are attempting to elucidate the relative contribution of genes and environmental factors in its causation. Major progresses have been made, but new discoveries lead to many more questions than answers. The role of UVR in melanoma has long been known, but this association is very complex to dissect. Host responses to UVR, as well as important genes involved in the cell cycle and senescence, such as p16 or CDKN2A, are leading

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