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Hi, need to submit a 1750 words essay on the topic Melanoma.

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Exposure to ultraviolet rays (UVA &amp. UVB) rank as the most important factors for development of melanomas. This effected through DNA damage, specifically thymine dimerization leading to oncogenic mutations. It is well known that the incidence of melanoma in Queensland, Australia (50/100,000) is five times that of the UK (10,000), despite the fact that the nearly all cases in Australia occur in people of Scottish and Irish descent. This clearly points out to solar exposure as the prime factor in it causation. Although tanning beds (Berwick 507) and sunscreens have been implicated as a possible causative factor, no significant statistical evidence has been presented yet. Additional risk is also seen in red-headed and fair-skinned people, people with multiple dysplastic or atypical naevi, and in a condition called congenital giant melanocytic naevi.

1. Germline Mutations : Apart from the fact that melanoma clusters can be seen in certain families, and melanoma-prone families are well known to have mutations in CDKN2A, CDK4 and other genes. The p16 gene mutation has also been reported in over 25% of familial melanomas worldwide, as well as in about 10 % of sporadic melanomas. It has a low degree of penetrance, and it is likely that sporadic melanoma has a complex pattern of inheritance.

Melanoma also has an association with various cancer family syndromes, most notably pancreatic cancer, but also in breast, throat and gastro-intestinal cancers.

2. Somatic mutations : A genetic progression model of the step-by-step transformation of precursor lesions (naevi) to melanomas, or the stages of melanoma progression itself have shown that there are important genetic loci where were changes accumulate. They are mostly due to loss of chromosomal material on multiple loci : chromosomes 1,3,6,9,10,11 and 17 being particularly affected. Somatic mutations on the BRAF gene has also been described in up to 60 % of melanomas.

3. The genetics of the at-risk phenotype : Over the past two decades, as it has become clearer that the fair skin-type and high naevus counts are powerful predictors of melanoma, the hunt for susceptible genes in these at-risk phenotypes has begun.

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