Association may be iatrogenicBMJ 1995; 311 doi: https://doi.org/10.1136/bmj.311.7007.750 (Published 16 September 1995) Cite this as: BMJ 1995;311:750
EDITOR,--Johanna Adami and colleagues postulate that exposure to ultraviolet light causes immunosuppression and, thereby, non-Hodgkin's lymphoma.1 To support their hypothesis they report that patients with non-Hodgkin's lymphoma had a relative risk of 5.5 of developing squamous cell skin cancer. Conversely, patients with squamous cell skin cancer had a twofold excess risk of developing non-Hodgkin's lymphoma or the closely related chronic lymphocytic leukaemia. The relation between ultraviolet light and non-Hodgkin's lymphoma was therefore examined only indirectly.
Patients with non-Hodgkin's lymphoma are often treated with drugs, notably alkylating agents, that are inherently mutagenic. Although Adami and colleagues highlight the immunosuppressive effects of these agents, they do not mention their mutagenicity. In support of the importance of the latter mechanism of action, the authors show that patients with non-Hodgkin's lymphoma have an increased general risk of malignancy of 1.2 times normal (95% confidence interval 1.1 to 1.3), a finding referred to as “close to the expected” in their abstract. Indeed, this figure can be expected to rise with time as the latent period after chemotherapy for myeloid and lymphoid malignancies is shorter than that for most of the common solid tumours.2
It has been a puzzle for many years that immunocompromised transplant recipients are predisposed to develop only two types of malignancy, skin cancer and non-Hodgkin's lymphoma. Most of the cases of non-Hodgkin's lymphoma are caused by uncontrolled proliferation of lymphocytes infected with Epstein-Barr virus. Furthermore, lesions of non-Hodgkin's lymphoma in patients immunocompromised by HIV infection have been shown to contain the newly described herpesvirus-like agent that has been postulated to cause Kaposi's sarcoma.3 This agent has now been reported in non-Kaposi's sarcoma skin lesions, notably squamous cell carcinoma, in transplant recipients.4
I find Adami and colleagues' explanation of their findings implausible. Alternative explanations are, firstly, the mutagenicity of agents used to treat non-Hodgkin's lymphoma and, secondly, infection with an agent that predisposes to malignant transformation in both skin and lymphoid cells.