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Genetics of Skin Cancer (PDQ®): Genetics - Health Professional Information [NCI] - Melanoma

Introduction

Both rare, high-penetrance and common, low-penetrance genetic factors for melanoma have been identified, and approximately 5% to 10% of all melanomas arise in multiple-case families. However, a significant fraction of these families do not have detectable mutations in specific susceptibility genes. The frequency with which multiple-case families are ascertained and specific genetic mutations are identified varies significantly between populations and geographic regions. A major population-based study has concluded that the high-penetrance susceptibility gene CDKN2A does not make a significant contribution to the incidence of melanoma.[1]

Risk Factors for Melanoma

Sun exposure

Sun exposure is the major known environmental factor associated with the development of skin cancer of all types. There are different patterns of sun exposure associated with each major type of skin cancer: basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma.

While there is no standard measure, sun exposure has generally been classified as intermittent or chronic, and its effects may be considered short-term or cumulative. Intermittent sun exposure is, by definition, sporadic, and is commonly associated with recreational activities, particularly among indoor workers who use weekend or vacation time to be outdoors and whose skin has not adapted to the sun. Chronic sun exposure is incurred by consistent, repetitive sun exposure, usually during outdoor work or more extensive recreational activities. Acute sun exposure is obtained over a short time on skin that has not adapted to the sun. Depending on the time of day and the skin type of the individual, acute sun exposure may result in sunburn. In epidemiology studies, sunburn is usually defined as an injury associated with pain and/or blistering that lasts for 2 or more days. Cumulative sun exposure is the additive amount of sun exposure that one receives over a lifetime. The impact of cumulative sun exposure likely reflects the additive effects of intermittent sun exposure or chronic sun exposure, or both.

Different patterns of sun exposure appear to lead to different types of skin cancer among susceptible individuals. Intermittent sun exposure seems to be the most important risk factor for melanoma.[2,3] Analytic epidemiologic studies have shown only modest risks related to sun exposure in melanoma development; three systematic reviews have demonstrated similar estimates for the role of intermittent sun exposure (i.e., odds ratios [ORs] of 1.6 to 1.7).[4,5,6] Chronic sun exposure, as observed in those occupationally exposed to sunlight, is either protective or without increased risk for the development of melanoma (see Table 5). The biological mechanisms underlying these differences in melanoma risk by sun exposure type have not been fully elucidated.

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