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Original Investigation
December 19, 2018

Risk Factors of Subsequent Primary Melanomas in Austria

Author Affiliations
  • 1Department of Dermatology, Medical University of Vienna, Vienna, Austria
  • 2Clinical Institute for Laboratory Medicine, Medical University of Vienna, Vienna, Austria
  • 3Department of Dermatology and Venereology, Medical University of Graz, Graz, Austria
  • 4Department of Blood Group Serology and Transfusion Medicine, Medical University of Vienna, Vienna, Austria
JAMA Dermatol. Published online December 19, 2018. doi:10.1001/jamadermatol.2018.4645
Key Points

Question  Which factors influence the risk of developing subsequent melanomas after first melanoma?

Findings  In this case-control study of 1648 patients with melanoma, odds ratios for CDKN2A mutations, nonmelanoma skin cancer, number of nevi, and actinic damage on the back were associated with multiple primary melanomas. Patients with many nevi were younger at the time of the diagnosis of their first melanoma.

Meaning  In patients with increased risk of multiple melanomas, current follow-up intervals should be adapted to prevent delayed diagnosis, and patients should be informed to raise awareness about improving sun protection and to encourage self-examination.


Importance  Information on risk factors of subsequent melanomas would be helpful to identify patients at risk after the diagnosis of their first melanomas.

Objective  To determine risk factors of subsequent melanomas.

Design, Setting, and Participants  In this retrospective case-control study, 1648 participants with histologically verified cutaneous melanoma diagnosed from January 1, 1968, though March 16, 2015, were recruited from a tertiary referral center as part of the Molecular Markers of Melanoma study. CDKN2A was sequenced in 514 and MC1R in 953 participants. Data were analyzed from March 7, 2008, through March 25, 2015.

Main Outcomes and Measures  Phenotypic traits and internal and external risk factors for the development of a second, third, or fourth melanoma.

Results  In total, 1648 patients (53.6% men; mean [SD] age, 54 [15] years) were enrolled, including 1349 with single and 299 with multiple primary melanoma. Mean (SD) age at recruitment was 57 (15) years for the single-melanoma and 62 (14) years for the multiple-melanoma groups. From the internal risk factors, family history (odds ratio [OR], 1.76; 95% CI, 1.22-2.55; P = .006), CDKN2A high-risk mutations (OR, 4.03; 95% CI, 1.28-12.70; P = .02), and high numbers of nevi as a phenotypic risk factor (ORs, 2.23 [95% CI, 1.56-3.28, P < .001] for 20-30 smaller nevi and 2.56 [95% CI, 1.50-4.36; P = .003] for 20-30 larger nevi) were significantly associated with the risk of developing a subsequent primary melanoma using multivariate logistic regression analysis. Nonmelanoma skin cancer (OR, 2.57; 95% CI, 1.84-3.58; P < .001) and signs of actinic skin damage, particularly on the back (ORs, 1.91 [95% CI, 1.12-3.25; P = .04] for freckling and 1.92 [95% CI, 1.29-3.08; P = .007] for solar lentigines), additionally increased risk of a subsequent melanoma. All those factors were also associated with an earlier development of the second melanoma. Patients with 3 melanomas developed their second melanoma earlier than patients with only 2 melanomas (mean [SD] age, 55 [15] years for those with 2 primary melanomas; 52 [15] years for those with 3 primary melanomas). Time spent outdoors, solarium use, outdoor occupation, and hair color had no significant associations in these models.

Conclusions and Relevance  According to the results of this study, internal factors (family history and genetic variants), number of nevi, and actinic damage on the back are more relevant for the development of subsequent melanomas than skin phototype or hair color. Patients with many nevi were younger at the time of the diagnosis of their first melanoma. This finding could help to identify persons at increased risk of developing multiple primary melanomas.