Methotrexate may be Linked to Higher Risk of Skin Cancers

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A new study published in the British Journal of Cancer found that methotrexate (MTX) could be a risk factor for 3 types of skin cancer: basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (cSCC), and cutaneous malignant melanoma (CMM).¹ MTX was only found to present an increased risk for basal cell carcinoma for patients who take the drug for mild to severe psoriasis.

The study was a result of a research collaboration between the University of Southern Denmark, Aarhus University, and the University of Copenhagen. Study authors analyzed patient health records from Nordic countries between 2004 and 2018, and identified 

• 131,447 patients with basal cell carcinoma
• 18,661 patients with squamous cell carcinoma
• 26,068 patients with cutaneous malignant melanoma

Every patient with skin cancer was compared with 10 age and sex-matched controls. Study findings showed that, at a group level, it was more common for patients who developed any of the 3 types of skin cancer to have been treated with MTX previously. Study authors found that an increased risk of developing any of the 3 skin cancers after taking MTX was

• 20%-38% for BCC
• 37% to 89% for cSCC
• 13% to 61% for CMM

Patients who were treated with higher levels of MTX were found to be at a higher rate for cSCC and BCC, but not for CMM. First study author Sam Polesie, PhD, associate professor of dermatology and venereology at Sahlgrenska University Hospital at the University of Gothenburg said the study shows the absolute risk for an individual patient, developing any of these skin cancer types, remains small even if they use the drug.

The researchers acknowledge the limitations of this study, which was confined to patients with psoriasis. They found no statistical correlation between MTX and an increased risk of cSCC or melanoma but did find an increase in the risk of developing BCC. Polesie said that sun exposure habits and the use of light therapies were not factored into this research, and the study was also conducted only on patients in Nordic countries, who typically have skin types 1 and 3. The authors say clinicians should not consider skin cancer risk an important consideration when prescribing MTX, but that further studies are needed to include data on UV exposure.

Reference

1. Polesie S, Gillstedt M, Schmidt S, et al. Use of methotrexate and risk of skin cancer: a nationwide case–control study. British Journal of Cancer (2023). doi.org/10.1038/s41416-023-02172-7