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S. Elizabeth Whitmore, MD, ScM

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Stern's report, "Lymphoma Risk in Psoriasis: Results of the PUVA Follow-up Study,"¹ is extremely interesting and beckons us to question "Why?" and "Should we be doing anything differently for our patients being treated with methotrexate?" Stern examined the cohort of 1380 patients initially treated with psoralen–UV-A from 1975 through 1976 and found that the incidence of lymphoma was increased in the subgroup of patients who had been exposed to high levels of methotrexate (incidence rate ratio, 4.39; 95% confidence interval, 1.59-12.06).

One cannot help but wonder how this might relate to folate metabolism, folate stores, and homocysteine levels. Folate metabolism plays an essential role in DNA synthesis and methylation. Genetic polymorphisms that lead to elevated homocysteine levels have been investigated and linked to increased risk of lymphoma, acute lymphoblastic leukemia, and colorectal cancer.²

The most common genetic cause of hyperhomocysteinemia is a methylenetetrahydrofolate reductase (. . . [Full Text of this Article]

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RELATED LETTER

Methotrexate and Risk for Lymphoma—Reply
Robert S. Stern
Arch Dermatol. 2007;143(5):664.
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