Methotrexate Exposure and Risk of Cutaneous Malignant Melanoma: No Evidence of a Dose-response Relationship

Methotrexate treatment has been linked with an increased risk of melanoma. However, a possible dose-response relationship with respect to methotrexate exposure and melanoma has not been addressed. The aim of the present study was to investigate whether higher accumulated doses of methotrexate correlate with an increased risk of melanoma, which would further support a possible association. A nationwide retrospective cohort study was conducted. All Swedish patients over 18 years of age who were dispensed methotrexate in the period 2005 to 2014 were registered (n = 101,966) and matched to the cancer registry. A Cox proportional hazards model, testing risk of melanoma vs. total accumulated methotrexate dose, controlled for sex, age group, and time from first to last dispensed prescription of methotrexate, yielded no significant risk dependence on dose, and a hazard ratio of 1.02 (95% CI 0.97-1.08). Overall, no conclusive dose-response relationship was observed between methotrexate exposure and risk of melanoma.