Melanoma is a highly lethal form of skin cancer. It is mainly caused by ultraviolet (UV) radiation-induced DNA damage in melanocytes. While sunlight is the most common source of UV exposure, artificial UV from indoor tanning beds has emerged as a main and preventable risk factor. Epidemiological studies have continuously shown that tanning bed use elevates melanoma risk, which leads to earlier disease onset and disproportionately affects young women. Indoor tanning remains widely used despite strong warnings from public health organizations and classification of tanning beds as a group 1 carcinogen. There is a key gap to understand on how tanning bed exposure changes melanocytes at the molecular level and whether it creates distinct mutational patterns that explain the characteristic clinical presentation of tanning bed-associated melanoma, which increases on body sites with low cumulative sun exposure and often manifests as many primary tumors.
The aim of this study was to evaluate how indoor tanning influences melanoma risk by integrating large-scale epidemiological data with single-cell molecular analyses. This study also assessed whether tanning bed use increases melanoma incidence, changes the anatomic distribution of melanoma, increases mutation burden in normal melanocytes, and induces distinct mutational signatures or pathogenic mutations that predispose cells to malignant transformation.
The epidemiological component analyzed medical records from over 32,000 dermatology patients at Northwestern University. About 3000 individuals with a quantified history of tanning bed use (≥10 sessions) were compared with an age-matched control group of nonusers. Melanoma incidence, dosage response relationships, anatomic distribution, and multiple primary melanomas were assessed by using chi-square tests and multivariate logistic regression adjusted for age, sex, sunburn history, and family history of melanoma.
Normal skin biopsies were collected from 11 heavy tanning bed users, matched with clinic-based controls with no tanning history, and an additional control group of cadaver donors, intended to represent the general population for molecular analyses better. Single melanocytes were isolated, clonally expanded, and subjected to whole exome and RNA sequencing. Rigorous bioinformatic pipelines were used to eliminate amplification artifacts and detect somatic mutations with high specificity and sensitivity. Mutation burden, UV-related mutational signatures, pathogenic driver mutations, clonal relationships, and gene expression variations were analyzed. Statistical models involving linear mixed effects and robust mixed effects models were applied to control for donor variability and anatomical site.
Epidemiological analyses showed that tanning bed users had more than double the incidence of melanoma as compared to nonusers (5.1% vs. 2.1%). Tanning bed use was linked with nearly a 3-fold elevated melanoma risk with a clear dose-response relationship as tanning sessions increased after adjustment for confounding factors. Melanomas in tanning bed users were likely to increase on body sites with low cumulative sun exposure and often had many primary tumors.
Melanocytes from tanning bed users exhibited twice the mutation burden of those from control donors at the molecular level. There is a difference that remained significant after accounting for anatomical site and donor-specific effects. The effect was specifically pronounced on the lower back, a region minimally exposed to natural sunlight but fully exposed during tanning. UV-associated mutational signature SBS7 dominated in both cohorts, which confirms UV radiation as the primary mutagen. SBS11 was significantly more prevalent in tanning bed users, appearing in most tanning donors but rarely in controls. SBS11 resembles UV-induced mutations, but changes in trinucleotide context and its etiology remain unknown, though melanoma is the cancer most linked with it.
Melanocytes from tanning bed users were substantially more likely to harbor pathogenic, melanoma-associated mutations, specifically in genes involved in MAPK signaling, like NF1. Clonal fields of related melanocytes were more common in biopsies with high mutation burdens, which suggests expanded populations of at-risk precursor cells. Gene expression analysis revealed modest differences between cohorts, including up-regulation of APOBEC3B in tanning bed melanocytes, though the biological significance of these changes requires further investigation.
This study shows that indoor tanning significantly increases melanoma risk by increasing mutation burden and affecting melanocyte susceptibility to cancer. Tanning beds expose more skin area to intense UV radiation, which causes broader mutagenesis, such as familial melanoma syndrome. Key results include SBS11 enrichment and heightened pathogenic mutations, disproving claims that tanning beds are safer than sunlight. The results underscore unique mutational effects of tanning beds on melanocytes, which reinforce public health warnings and explain distinct melanoma patterns in users.
Reference: Gerami P, et al. Molecular effects of indoor tanning. Sci Adv. 2025;11:eady4878. doi:10.1126/sciadv.ady4878
