Immunosuppressive Medications and Squamous Cell Skin Carcinoma: Nested Case-Control Study Within the Skin Cancer after Organ Transplant (SCOT) Cohort

Am J Transplant. 2016 Feb;16(2):565-73. doi: 10.1111/ajt.13596.

Abstract

Organ transplant recipients (OTRs) have a substantially elevated risk of squamous cell skin carcinoma (SCSC), largely attributed to immunosuppressive medications used to prevent graft rejection, although data to support the role of newer drugs in SCSC risk are sparse. We investigated the association between immunosuppressive medications and SCSC risk among cardiac and renal transplant recipients in the SCOT cohort study. Incident cases were ascertained through medical record review after self-report of skin biopsy (n = 170). Controls without SCSC (n = 324) were matched to cases on sex, age, race, transplant year, hospital, donor type, organ transplanted, and time between transplantation and interview. Conditional logistic regression was used to evaluate the association between specific medications and SCSC. Users of the antimetabolite azathioprine were more than twice as likely to develop SCSC (odds ratio [OR] = 2.67, 95% confidence interval [CI] 1.23-5.76). In contrast, the newer antimetabolite preparations (i.e., mycophenolic acid [MPA]) were associated with lower SCSC risk (OR = 0.45, 95% CI 0.29-0.69). This inverse association between MPA and SCSC persisted among OTRs with no history of azathioprine use, even after adjustment for simultaneous use of the calcineurin inhibitor tacrolimus (OR = 0.52, 95% CI 0.32-0.84). Our data suggest that the increased risk of SCSC historically associated with azathioprine is not seen in OTRs prescribed newer regimens, including MPA and tacrolimus.

Keywords: cancer, malignancy, neoplasia; clinical research, practice; immunosuppression, immune modulation; skin, nonmelanoma, epidemiology.

Publication types

  • Comparative Study

MeSH terms

  • Antibiotics, Antineoplastic / therapeutic use
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / epidemiology
  • Case-Control Studies
  • Cohort Studies
  • Female
  • Follow-Up Studies
  • Graft Rejection / epidemiology
  • Graft Rejection / prevention & control*
  • Graft Survival
  • Heart Transplantation*
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Incidence
  • Kidney Transplantation*
  • Male
  • Middle Aged
  • Mycophenolic Acid / therapeutic use
  • Postoperative Complications / prevention & control*
  • Prognosis
  • Risk Factors
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / epidemiology
  • Tacrolimus / therapeutic use
  • Washington / epidemiology

Substances

  • Antibiotics, Antineoplastic
  • Immunosuppressive Agents
  • Mycophenolic Acid
  • Tacrolimus