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Inherited susceptibility to melanoma

Hensin Tsao, MD, PhD
Linda Rodgers, MGC, CGC
Devanshi Patel, MS, CGC
Section Editors
Michael B Atkins, MD
Benjamin A Raby, MD, MPH
Deputy Editor
Michael E Ross, MD


The etiology of all cancers depends upon the interplay between environmental and genetic factors.

For melanoma, the most significant environmental risk factor is solar ultraviolet (UV) radiation exposure [1]. However, this risk is greatly influenced by genetic factors. As an example, skin type, a heritable trait, modifies the risk presented by a given amount of solar exposure. Dark-skinned populations have a much lower incidence of melanoma than fairer-skinned populations exposed to equivalent sunlight. In the United States, the risk of melanoma in African-Americans is approximately 10 percent of that in Caucasians.

A study of familial risk and hereditability identified 23,980 people who had cancer and were twins [2]. The risk of concordance for melanoma was much greater than the general population, and it was estimated that 58 percent of the risk was inherited.

Significant progress has been made toward understanding the genes that contribute to inherited susceptibility for melanoma in some patients [3]. Uncommon, but high-risk, alleles contribute to the hereditary cancer phenotype that includes multiple cases of the associated cancer or cancers on one side of the family, multiple primary cancers in a given individual, and early age of onset for a given cancer. With further advances in both genomic technologies and the conceptual framework to isolate more prevalent, but lower risk, alleles, the spectrum of genetic lesions that contribute to melanoma risk can be expected to broaden.

The genetic risk factors for melanoma are discussed here, along with potential implications for genetic screening. Other risk factors associated with the development of melanoma are discussed separately. (See "Risk factors for the development of melanoma".)


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