Melanoma Tumor Mutational Burden and Indoor Tanning Exposure.

Importance: UV-induced mutagenesis leads to a higher tumor mutational burden (TMB) in cutaneous melanoma relative to other cancer types. TMB is an important prognostic marker in advanced melanoma; higher TMB is associated with greater clinical response to immune checkpoint inhibition and improved survival.

Objective: To evaluate the association between cutaneous melanoma TMB and indoor tanning exposure, as well as other demographic, dermatologic, and tumor characteristics.

Design, setting, and participants: This retrospective cohort study took place at Dana-Farber Cancer Institute, a tertiary-care cancer treatment center in Boston, Massachusetts, between 2013 and 2022. Patients with a diagnosis of cutaneous melanoma for whom next-generation sequencing data and tanning bed exposure history were available were included.

Exposures: Indoor tanning exposure history, tumor characteristics, demographics, and dermatologic history were collected via retrospective medical record review.

Main outcomes and measures: The association of tanning bed use with TMB was modeled using inverse probability of treatment weighted, multivariable modeling.

Results: Among 617 patients (median [IQR] age at diagnosis, 61 [50-71] years; 337 [62.9%] male), there was no association between indoor tanning exposure and TMB after adjustment for demographic, tumor, and dermatologic characteristics (yes vs no: log2 TMB [SE], 4.07 [0.44] vs 3.97 [0.45]; P = .39). However, there was a statistically significant association between higher TMB and older age at diagnosis, history of nonmelanoma skin cancer, and head and neck tumors relative to other primary sites. Average TMB was statistically significantly lower in patients with a history of abnormal nevi (yes vs no: log2 TMB [SE], 3.89 [0.44] vs 4.15 [0.44]; P = .01).

Conclusions and relevance: This cohort study suggests that indoor tanning exposure, while known to increase risk of melanoma, may not be meaningfully associated with melanoma TMB. Additional characteristics were associated with higher TMB and, thus, potentially improved immune checkpoint inhibitor response.