title: Cumulative immunosuppressant exposure is associated with diversified cancer risk among 14 832 patients with systemic lupus erythematosus: a nested case-control study.
abstract: Immunosuppressive therapy is necessary to alter the natural course of SLE. However, immunosuppressant-related cancer risk is a major concern. The aim of this study was to determine whether immunosuppressant use is associated with cancer risk in SLE.
  
  
  
  We designed a retrospective nested case-control study within an SLE population based on the National Health Insurance Research Database in Taiwan. We screened 14 842 patients with SLE from 2001 to 2013 and compared patients with SLE complicated by later cancer with patients with SLE but without cancer. The cumulative dose of immunosuppressants was calculated from the SLE diagnosis date to the occurrence of cancer. The immunosuppressants of interest were AZA, CYC, MTX, HCQ and systemic glucocorticoids. Adjusted odds ratios (ORs) for cancer were calculated in conditional Cox regression models after propensity score matching.
  
  
  
  The top five types of cancers were breast (16.9%), haematological (11.7%), colorectal (11.0%), lung (10.6%) and hepatobiliary (10.4%) cancers. After matching, this study included 330 cancer patients and 1320 matched cancer-free patients. The adjusted analyses showed an association of a higher cumulative CYC dose (OR = 1.09, 95% CI: 1.04, 1.13) and lower HCQ dose (OR = 0.93, 95% CI: 0.90, 0.97) with cancer risk in comparison with the controls.
  
  
  
  Diverse cancer risks are associated with different immunosuppressants in patients with SLE. CYC increases the risk of cancer, and HCQ decreases this risk in SLE patients, both in a dose-dependent manner.
authors.affiliation: Division of Rheumatology, Allergy, and Immunology, Department of Internal Medicine Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung.
authors.forename: Chung-Yuan
authors.initials: CY
authors.lastname: Hsu
authors.affiliation: Division of Cardiology, Chang-Gung Memorial Hospital, Yunlin.
authors.forename: Ming-Shyan
authors.initials: MS
authors.lastname: Lin
authors.affiliation: Division of Rheumatology, Allergy, and Immunology, Department of Internal Medicine Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung.
authors.forename: Yu-Jih
authors.initials: YJ
authors.lastname: Su
authors.affiliation: Division of Rheumatology, Allergy, and Immunology, Department of Internal Medicine Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung.
authors.forename: Tien-Tsai
authors.initials: TT
authors.lastname: Cheng
authors.affiliation: Division of Cardiology, Chang Gung Memorial Hospital, Chiayi.|School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan County.
authors.forename: Yu-Sheng
authors.initials: YS
authors.lastname: Lin
authors.affiliation: Division of Rheumatology, Allergy, and Immunology, Department of Internal Medicine Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung.
authors.forename: Ying-Chou
authors.initials: YC
authors.lastname: Chen
authors.affiliation: Division of Rheumatology, Allergy, and Immunology, Department of Internal Medicine Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung.
authors.forename: Wen-Chan
authors.initials: WC
authors.lastname: Chiu
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Keelung, Taiwan.
authors.forename: Tien-Hsing
authors.initials: TH
authors.lastname: Chen
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000139:chemically induced* / Q000453:epidemiology; D012189:Retrospective Studies; D012307:Risk Factors; D013624:Taiwan / Q000453:epidemiology
chemical_list: D007166:Immunosuppressive Agents
keywords: cancer; cyclophosphamide; hydroxychloroquine; lupus