In Australia where ultraviolet radiation is a daily companion, researchers uncovered distinct biological footprints for two types of melanomas, one that emerges from moles and another that forms independently.
Patients with a high mole count and elevated genetic risk may be more likely to develop melanoma that arises from moles, according to a large prospective cohort study conducted in Queensland, Australia.
Researchers followed 38,801 adult patients aged 40 to 69 years over a median of 11.4 years. During this period, 859 patients were diagnosed with invasive melanoma. Among these, 24.3% were nevus-associated, while 75.7% were de novo. Nevus-associated melanoma was more prevalent among males (129 cases) than females (80 cases), while de novo melanoma affected 362 males and 288 females.
A high mole count at age 21 was strongly associated with melanoma risk. Participants reporting had a hazard ratio (HR) of 6.86 (95% confidence interval [CI] = 3.82–12.33) for nevus-associated melanoma compared with those reporting no moles. The HR for many moles and de novo melanoma was 3.21 (95% CI = 2.23–4.63) (P = .001).
Individuals with the highest melanoma polygenic risk had an HR of 6.46 (95% CI =3.42–12.20), compared with 2.98 (95% CI = 2.21–4.02) for de novo melanoma (P = .006).
Nevus-associated melanomas were diagnosed at a younger age than de novo melanomas. The mean age at diagnosis was 62.8 years (SD, 8.4) for nevus-associated melanoma and 64.9 years (SD, 8.0) for de novo melanoma (P = .001). Mean tumor thickness was 0.58 mm (SD, 0.50) for nevus-associated cases and 1.02 mm (SD, 1.58) for de novo (P < .001).
Tumor location varied by sex and melanoma type. Among males with nevus-associated melanoma, 65.9% occurred on the trunk. In females, 31.3% were on the upper limbs and 30.0% on the lower limbs.
Both melanoma types were associated with sunburns and markers of actinic skin damage. Experiencing six to ten sunburns in adulthood increased the risk for both subtypes: HR was 1.69 (95% CI = 1.04–2.75) for nevus-associated melanoma and 1.76 (95% CI = 1.32–2.36) for de novo melanoma. No statistically significant differences in sun exposure–related risks were found between the two melanoma types.
Sex did not significantly modify the risk factor profiles for nevus-associated melanoma. However, older age had a stronger association with de novo melanoma in males than in females.
“These prospective findings, comprising genetic, phenotypic, and histologic data, confirm the distinct etiologic pathways for NAM vs de novo melanoma,” said Catherine M. Olsen, PhD, from QIMR Berghofer Medical Research Institute, Queensland, Australia, and one of the authors.
The study found that nevus-associated and de novo melanomas follow distinct etiologic pathways. High moles count and genetic predisposition were more strongly linked to nevus-associated melanoma, while both types were associated with cumulative sun exposure and skin damage.
Full disclosures can be found in the published study.
Source: JAMA Dermatology
