Nevus phenotype, genetics increase risk of second primary melanomas
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Second primary melanomas are more likely to develop in patients with more nevi and a high genetic predisposition to melanoma, according to a study.
“This study shows that people who develop two or more melanomas, on average, have higher nevus burden and higher genetic risk for melanoma than people who develop only one melanoma,” David C. Whiteman, MD, PhD, a senior scientist in the cancer control group at QIMR Berghofer Medical Research Institute in Herston, Queensland, Australia, told Healio. “This suggests that some people are ‘super-susceptible’ to the development of melanoma and are therefore predisposed to developing multiple primary melanomas during their lifetime.”
The population-based prospective cohort study included 38,845 patients (mean age at baseline, 56.1 years; age range, 40-69 years; 54.7% women) reporting white European ancestry. Each participant answered a baseline survey, while researchers calculated a polygenic risk score (PRS) for melanoma in a subset of patients (n = 15,381).
During a median-follow up period of 7.4 years, one primary melanoma was reported in 3.1% of participants, whereas two or more were reported in 0.6%. Additionally, a greater proportion of second primary vs. first primary melanomas were in situ (73.7% vs. 59.1%) and 1 mm or thinner (93.9% vs. 70.3%).
The researchers found a stronger association between second primary melanomas and high melanoma PRS (HR = 3.28; 95% CI, 2.06-5.23) compared with first primary melanomas (HR = 2.06; 95% CI, 1.71-2.49).
Additionally, participants with a second primary melanoma were significantly more likely to have nevus phenotype (adjusted HR = 6.36; 95% CI, 3.77-10.75) than those with only one primary melanoma (aHR = 3.46; 95% CI, 2.72-4.4).
Researchers also found that a history of multiple skin cancer excisions was more strongly associated with patients who had a second primary melanoma (aHR = 2.63; 95% CI, 1.8-3.83) than only a first primary melanoma (aHR = 1.86; 95% CI, 1.61-2.16).
Genetic predisposition and having more nevi are associated with the highest risk of developing second primary melanoma, according to the study. In fact, Whiteman emphasized that, “melanoma patients with a high-risk phenotype warrant continued surveillance for the development of second primary melanomas.”