title: Immunosuppression with mammalian target of rapamycin inhibitor and incidence of post-transplant cancer in kidney transplant recipients.
abstract: Evidence is limited regarding the effect of de novo therapy with mammalian target of rapamycin (mTOR) inhibitors on cancer risk after kidney transplantation.
  
  
  
  Collaborative Transplant Study data from 78 146 adult recipients of first deceased-donor kidney transplants (1999-2013) were analysed (4279 mTOR inhibitor, 73 867 no mTOR inhibitor) using standard methods. Propensity score matching was performed for analysis of basal cell and squamous cell skin cancer.
  
  
  
  Standardized incidence ratios (SIR) versus a matched non-transplant population showed reduced tumour incidence in recipients with de novo mTOR inhibitor therapy compared with no mTOR inhibitor for non-melanoma skin cancer (NMSC) (SIR 5.1 versus 6.1; P =0.019) but not non-NMSC cancers (SIR 1.6 versus 1.7; P =0.35). Within propensity score-matched groups (n = 4265), multivariable Cox regression analysis showed a trend to reduced NMSC with mTOR inhibition [hazard ratio (HR) 0.77; P =0.063] but not for all non-NMSC tumours (HR 0.94; P= 0.59). A significant effect for mTOR inhibition was observed for basal cell carcinoma of the skin (HR 0.56; P= 0.004) but not squamous cell carcinoma (HR 0.87; P= 0.54).
  
  
  
  De novo mTOR inhibition was associated with a substantially and significantly reduced risk of basal cell carcinoma of the skin after kidney transplantation. A significant reduction of the incidence of other cancers was not found.
authors.affiliation: Institute of Immunology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Opelz
authors.affiliation: Institute of Immunology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Unterrainer
authors.affiliation: Institute of Immunology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Caner
authors.initials: C
authors.lastname: Süsal
authors.affiliation: Institute of Immunology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Döhler
mesh_terms: D000328:Adult; D005260:Female; D005858:Germany / Q000453:epidemiology; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D015994:Incidence; D016030:Kidney Transplantation / Q000009:adverse effects*; D008875:Middle Aged; D009369:Neoplasms / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control*; D020123:Sirolimus / Q000627:therapeutic use*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D066027:Transplant Recipients
chemical_list: D007166:Immunosuppressive Agents; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus
keywords: kidney transplantation; malignancy; mammalian target of rapamycin; non-melanoma skin cancer