title: Lymphoma risk in systemic lupus: effects of disease activity versus treatment.
abstract: OBJECTIVE
  To examine disease activity versus treatment as lymphoma risk factors in systemic lupus erythematosus (SLE).
  
  
  METHODS
  We performed case-cohort analyses within a multisite SLE cohort. Cancers were ascertained by regional registry linkages. Adjusted HRs for lymphoma were generated in regression models, for time-dependent exposures to immunomodulators (cyclophosphamide, azathioprine, methotrexate, mycophenolate, antimalarial drugs, glucocorticoids) demographics, calendar year, Sjogren's syndrome, SLE duration and disease activity. We used adjusted mean SLE Disease Activity Index scores (SLEDAI-2K) over time, and drugs were treated both categorically (ever/never) and as estimated cumulative doses.
  
  
  RESULTS
  We studied 75 patients with lymphoma (72 non-Hodgkin, three Hodgkin) and 4961 cancer-free controls. Most lymphomas were of B-cell origin. As is seen in the general population, lymphoma risk in SLE was higher in male than female patients and increased with age. Lymphomas occurred a mean of 12.4 years (median 10.9) after SLE diagnosis. Unadjusted and adjusted analyses failed to show a clear association of disease activity with lymphoma risk. There was a suggestion of greater exposure to cyclophosphamide and to higher cumulative steroids in lymphoma cases than the cancer-free controls.
  
  
  CONCLUSIONS
  In this large SLE sample, there was a suggestion of higher lymphoma risk with exposure to cyclophosphamide and high cumulative steroids. Disease activity itself was not clearly associated with lymphoma risk. Further work will focus on genetic profiles that might interact with medication exposure to influence lymphoma risk in SLE.
authors.affiliation: Medicine, Division of Clinical Epidemiology, McGill University Health Centre, , Montreal, Quebec, Canada.
authors.forename: Sasha
authors.initials: S
authors.lastname: Bernatsky
authors.forename: Rosalind
authors.initials: R
authors.lastname: Ramsey-Goldman
authors.forename: Lawrence
authors.initials: L
authors.lastname: Joseph
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Boivin
authors.forename: Karen H
authors.initials: KH
authors.lastname: Costenbader
authors.forename: Murray B
authors.initials: MB
authors.lastname: Urowitz
authors.forename: Dafna D
authors.initials: DD
authors.lastname: Gladman
authors.forename: Paul R
authors.initials: PR
authors.lastname: Fortin
authors.forename: Ola
authors.initials: O
authors.lastname: Nived
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Petri
authors.forename: Soren
authors.initials: S
authors.lastname: Jacobsen
authors.forename: Susan
authors.initials: S
authors.lastname: Manzi
authors.forename: Ellen M
authors.initials: EM
authors.lastname: Ginzler
authors.forename: David
authors.initials: D
authors.lastname: Isenberg
authors.forename: Anisur
authors.initials: A
authors.lastname: Rahman
authors.forename: Caroline
authors.initials: C
authors.lastname: Gordon
authors.forename: Guillermo
authors.initials: G
authors.lastname: Ruiz-Irastorza
authors.forename: Edward
authors.initials: E
authors.lastname: Yelin
authors.forename: Sang-Cheol
authors.initials: SC
authors.lastname: Bae
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Wallace
authors.forename: Christine A
authors.initials: CA
authors.lastname: Peschken
authors.forename: Mary Anne
authors.initials: MA
authors.lastname: Dooley
authors.forename: Steven M
authors.initials: SM
authors.lastname: Edworthy
authors.forename: Cynthia
authors.initials: C
authors.lastname: Aranow
authors.forename: Diane L
authors.initials: DL
authors.lastname: Kamen
authors.forename: Juanita
authors.initials: J
authors.lastname: Romero-Diaz
authors.forename: Anca
authors.initials: A
authors.lastname: Askanase
authors.forename: Torsten
authors.initials: T
authors.lastname: Witte
authors.forename: Susan G
authors.initials: SG
authors.lastname: Barr
authors.forename: Lindsey A
authors.initials: LA
authors.lastname: Criswell
authors.forename: Gunnar K
authors.initials: GK
authors.lastname: Sturfelt
authors.forename: Irene
authors.initials: I
authors.lastname: Blanco
authors.forename: Candace H
authors.initials: CH
authors.lastname: Feldman
authors.forename: Lene
authors.initials: L
authors.lastname: Dreyer
authors.forename: Neha M
authors.initials: NM
authors.lastname: Patel
authors.forename: Yvan
authors.initials: Y
authors.lastname: St Pierre
authors.forename: Ann E
authors.initials: AE
authors.lastname: Clarke
mesh_terms: D000328:Adult; D000962:Antimalarials / Q000627:therapeutic use; D001379:Azathioprine / Q000627:therapeutic use; D016022:Case-Control Studies; D003520:Cyclophosphamide / Q000627:therapeutic use; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use; D006689:Hodgkin Disease / Q000453:epidemiology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy* / Q000453:epidemiology*; D008228:Lymphoma, Non-Hodgkin / Q000453:epidemiology*; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D012307:Risk Factors; D055815:Young Adult
chemical_list: D000962:Antimalarials; D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; D009173:Mycophenolic Acid; D001379:Azathioprine; D008727:Methotrexate
keywords: Disease Activity; Epidemiology; Systemic Lupus Erythematosus; Treatment