Risk Factors for Melanoma

  • Identifying risk factors and estimating an individual’s risk of developing melanoma can be clinically useful:
    • In determining primary prevention strategies and in directing the level of screening
  • Patients identified as being at high risk for melanoma:
    • May also be recruited to prevention trials
  • Multiple factors can place a patient at risk for developing melanoma:
    • Some factors are modifiable while others are inherent to the individual
  • Skin type:
    • Caucasians have at least 20 times the melanoma incidence of African Americans and five times the melanoma incidence of American Hispanics
    • In addition, white patients with red or blond hair, fair complexion, or blue eyes are at increased risk for melanoma
  • Age and Gender:
    • The incidence of melanoma increases with age
    • The incidence of melanoma is 1.7-fold higher for women than men before 49 years of age
    • Over age 70:
      • The incidence of melanoma is 2.4-fold higher for men than women
    • In general, the incidence of melanoma is higher in men than in women
    • Specifically, a man’s lifetime risk of melanoma development:
      • Is approximately 1.5 times greater than a woman’s risk
  • Overexposure to ultraviolet radiation (UVR) from the sun:
    • Overexposure of UVR from the sun has been associated with an increased risk of melanoma
    • Genetic sequencing data also support the role of UV melanomagenesis
    • Known to be a tumor with one of the highest mutational loads:
      • A seminal report of the melanoma effort within The Cancer Genome Atlas Program:
        • Revealed that a majority of somatic mutations in melanoma indeed have a “UV signature”
    • Data support that damage from sunburns in childhood or even in adulthood are associated with increased risk:
      • A correlation has been identified between the number of severe and painful sunburn episodes and the risk of melanoma:
        • For example, patients who have a history of more than 10 severe sunburns:
          • Are more than twice as likely to develop a melanoma compared to patients who have no history of sunburns
  • Use of indoor tanning devices:
    • Multiple studies support that use of an indoor tanning device is strongly also associated with increased risk of melanoma
    • A systematic review by the International Agency for Research on Cancer (IARC) demonstrated:
      • A 15% increased relative risk of melanoma in individuals who had ever used a sunbed versus those who had never (RR 1.15; 95% CU 1.00 to 1.31)
    • The dangers of indoor tanning have been corroborated by subsequent US and Australian groups
    • Young age of onset and higher frequency of use are key risk factors that are associated with even greater risk of melanoma
    • Indeed, a well-designed Minnesota case–control study showed increased risk with number of years, hours, and sessions of indoor tanning, independent of outdoor sun exposure:
      • These researchers also found that 97% of women diagnosed with melanoma before age 30 had indoor tanned
    • An Australian population-based study showed that tanning bed use more than 10 times per year:
      • Was associated with a doubling of melanoma risk in patients at least 30 years of age, and the association was stronger with earlier exposure
    • Young patients who use indoor tanning devices more than 10 times annually have more than 7 times the melanoma risk compared to individuals who do not indoor tan
    • A recent meta-analysis estimated a 1.8% increased melanoma risk for each additional tanning bed session
    • Since 2009, the World Health Organization lists tanning beds as:
      • A Class I carcinogen
  • Previous melanoma:
    • Individuals with a personal history of melanoma have an increased risk of developing a second melanoma of:
      • Approximately 3% to 7% (life time risk)
  • Benign nevi:
    • Although a benign nevus is most likely not a precursor of melanoma, the presence of large numbers of nevi has been consistently associated with an increased risk of melanoma:
      • Persons with ≥ 50 nevi, all of which are > 2 mm in diameter:
        • Have 5 to 17 times the melanoma risk of persons with fewer nevi
    • Individuals who tend to develop freckles also have an increased risk of melanoma
  • Family history:
    • Approximately 10% of individuals diagnosed with melanoma have a family member with a history of melanoma
    • A family history of melanoma increases an individual’s risk of melanoma three- to eightfold
    • Furthermore, persons who have two or more family members with melanoma are also at a particularly high risk
  • Genetic predisposition:
    • Approximately 8% to 12% of melanomas occur in individuals with a genetic predisposition
    • Specific genetic alterations have been implicated in the pathogenesis of melanoma:
      • Cyclin-dependent kinase inhibitor 2A (CDKN2A):
        • Is the most commonly identified mutation in suspected familial melanoma:
          • A tumor suppressor gene located on chromosome 9p21:
            • CDKN2A is probably involved in familial and sporadic cutaneous melanoma
        • Data from North America, Europe, and Australia correlate germline CDKN2A mutation (45%, 57%, and 20%, respectively):
          • With multiple-case families
          • Early age of onset
          • Multiple primaries within an individual patient
      • Deletions or rearrangements of chromosomes 10 and 8p are also well documented in cutaneous melanoma
      • Also associated with an increase in melanoma incidence are copy number gains of:
        • Chromosomes 2, 6p, 7, 8, 17, 19, and 20
          • These melanomas also tend to present at an earlier age and individuals may have multiple primary lesions
  • Atypical mole and melanoma syndrome:
    • Previously known as dysplastic nevus syndrome, atypical mole and melanoma syndrome is characterized by:
      • The presence of multiple, large (> 5 mm) atypical dysplastic nevi generally in nonexposed areas of skin that represent a distinct clinicopathologic type of melanocytic lesion
    • Melanomas can originate from either normal skin or from a dysplastic nevus
    • Since the actual frequency of an atypical mole progressing to melanoma is small:
      • Resection of all dysplastic nevi is not indicated
    • However, new, changing, or symptomatic lesions:
      • That appear suspicious for melanoma on clinical and / or dermoscopic examination:
        • Should be evaluated histologically

#Arrangoiz #CancerSurgeon #SurgicalOncologist #HeadandNeckSurgeon #CASO #CenterforAdvancedSurgicalOncology #Teacher #SkinCancer #Melanoma

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