(HealthDay News) — Methotrexate use may be associated with an increased risk of skin cancer, but more research is needed, according to an article published in the British Journal of Cancer.

Researchers found that methotrexate use was associated with an increased risk of basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (cSCC), and cutaneous malignant melanoma (CMM). However, the association with CMM and cSCC disappeared when the researchers restricted their analysis to patients with psoriasis, which suggests that surveillance bias and/or confounding by indication may have influenced the results.

For this study, the researchers used Danish health and demographic registries to identify all cases of BCC, cSCC, and CMM from 2004 to 2018. They identified 131,447 cases of BCC, 18,661 cases of cSCC, and 26,068 cases of CMM. They matched 10 control individuals to each case based on sex and birth year and compared methotrexate use between the groups.

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Methotrexate use was associated with an increased risk for BCC (adjusted odds ratio [aOR], 1.29; 95% CI, 1.20-1.38), cSCC (aOR, 1.61; 95% CI, 1.37-1.89), and CMM (aOR, 1.35; 95% CI, 1.13-1.61). For BCC and cSCC, the risk increased with higher cumulative doses of methotrexate.

When the study population was limited to patients with psoriasis, the aOR was 1.43 (95% CI, 1.23-1.67) for BCC, 1.18 (95% CI, 0.80-1.74) for cSCC, and 1.15 (95% CI, 0.77-1.72) for CMM.

“[W]e observed evidence of a dose-dependent increase in risks of BCC and cSCC, but not CMM, associated with use of MTX [methotrexate],” the researchers wrote. “However, the observed associations were of limited magnitude, and supplementary analyses suggested that confounding and surveillance bias played a role. At present, our findings therefore cannot support that skin cancer risk should be an important consideration when prescribing MTX. However, our findings do deserve further attention for future investigations that would ideally include data on UV exposure.”

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