Azathioprine, a drug used to treat a variety of conditions, may contribute to skin cancer development, according to a recent study in Nature Communications
Azathioprine is used to treat inflammatory bowel disease, arthritis, and vasculitis, as well as to prevent organ rejection in transplant patients. Azathioprine is known to cause increased photosensitivity to UVA light, but the new findings indicate an association between the drug and the mutational signature found in cases of cutaneous squamous cell carcinoma (cSCC).
More than 1 million new cases of cSCC are diagnosed annually in the United States. Although many cases are effectively treated with surgery or radiotherapy, there are few effective therapies for advanced cSCC. 
The researchers conducted a mutational signature analysis of cSCC tumors from 37 patients, many of whom had been on azathioprine. They found a new mutational signature, signature 32, which correlated with time on azathioprine therapy, according to the study.
Signature 32 was prominent among many of the samples from immunosuppressed patients, indicating a potential association with exposure to immunosuppressant drugs. Although most of the immunosuppressed patients who received azathioprine were also taking at least 1 other immunosuppressive drug, 3 of the tumors with signature 32 were from patients who had received azathioprine alone. Immunosuppressive patients who had not received azathioprine did not exhibit the mutational signature 32.
“There is a significant association only between a confirmed history of azathioprine exposure and the presence of signature 32 and not exposure to the other immunosuppressant drugs,” the researchers wrote in the study.
However, the researchers noted that the risks do not necessarily warrant the withdrawal of azathioprine. 
“As with all medications the risks must be balanced against the benefits, particularly with the need to treat potentially life-threatening diseases with an effective drug,” Charlotte Proby, MD, professor of dermatology in the School of Medicine at Dundee, said in a press release. “It is important that sun protection, skin surveillance, and early diagnosis/lesion removal are part of the routine management of patients on azathioprine.”
The findings provide insights into the complex molecular landscape of cSCC and highlight the potential targets that may be developed for future therapeutic approaches, according to the researchers.
Because of the small patient population in the study, further research with a larger independent cohort is needed to verify the findings. However, the researchers noted that the study provides evidence for an association between the novel mutational signature and long-term azathioprine use.

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Inman GJ, Wang J, Nagano A, Alexandrov LB, et al. The genomic landscape of cutaneous SCC reveals drivers and a novel azathioprine associated mutational signature. Nature Communications. 2018.
Study links widely-used drug azathioprine to skin cancers [news release]. University of Dundee. Accessed September 10, 2018.