The mutation burden of narrowband ultraviolet B phototherapy (NB-UVB) in human skin; relevance to NB-UVB lifetime exposures and skin cancer surveillance.

Abstract

Background: Ultraviolet radiation (UVR) is used as treatment for psoriasis and other skin diseases, but UVR can induce DNA mutations which may lead to skin cancer development. While skin cancers have been documented in patients treated with phototherapy, a limited number of epidemiological studies have examined skin cancer incidence in people receiving narrowband ultraviolet B (NB-UVB) treatment. Information on mutagenicity of NB-UVB would help inform about the potential skin cancer risks of this treatment.

Objectives: To determine the mutation burden in human skin resulting from a NB-UVB treatment course and use this data to estimate the total number of NB-UVB exposures whereupon skin cancer surveillance should commence.

Methods: Biopsies of normal skin were obtained before and after a course of NB-UVB from 16 patients with psoriasis. Epidermal DNA was sequenced using nanorate sequencing (NanoSeq) to determine the mutational signatures and mutation burden from NB-UVB.

Results: The NB-UVB treatment course increased the number of mutations in skin. Median increase in mutation burden was 0.55 substitutions/Mb in infrequently sun-exposed (buttock) and 0.89 substitutions/Mb in frequently sun-exposed (forearm) skin, P= 0.0001, n=14 patients and P=0.0098, n=10 patients respectively. Change in mutation burden due to NB-UVB ranged from 1.16 to 10.5-fold in buttock skin and 0.93 to 2.33-fold in forearm skin. This increase was mainly attributable to UVR-exposure linked mutational signatures, SBS7a and SBS7b, with some evidence that mutational burden related to genetic background of the individual. Modelling the change in mutation burden from NB-UVB relative to minimal erythema dose (MED) in comparison with average mutation burden in keratinocyte skin cancers allowed estimation of total lifetime exposures at which patients are likely to require skin cancer surveillance; for patients with MED equal to 2 standard erythemal doses (SEDs), skin cancer surveillance should be offered at 422, 165 and 58 NB-UVB exposures for those receiving low, typical, and high levels of sun exposure, respectively.

Conclusions: A treatment course of NB-UVB causes UVR-induced mutations in normal skin of patients with psoriasis. Relating mutation burden to MED and sun behaviour habits allows estimation of when to commence skin cancer surveillance according to total lifetime NB-UVB exposures.