Current PerspectiveGenetic epidemiology of melanoma
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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2020, Surgical Clinics of North AmericaCitation Excerpt :The mode of inheritance seems to be autosomal dominant with high penetrance. Individuals with deleterious germline mutations in these genes not only have multiple nevi and increased likelihood of melanoma at a young age,19 but also have a significantly increased risk for pancreatic cancer (see Table 2).9 Depending on the study, the relative risk of pancreatic cancer has been estimated to range between 9.420 and 47.8.21,22
Genetic polymorphisms in DNA repair and oxidative stress pathways associated with malignant melanoma susceptibility
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