The relationship between cancer and medication exposures in systemic lupus erythaematosus: a case–cohort study
Identifieur interne : 001C00 ( Istex/Corpus ); précédent : 001B99; suivant : 001C01The relationship between cancer and medication exposures in systemic lupus erythaematosus: a case–cohort study
Auteurs : S. Bernatsky ; L. Joseph ; J-F Boivin ; C. Gordon ; M. Urowitz ; D. Gladman ; P R Fortin ; E. Ginzler ; S-C Bae ; S. Barr ; S. Edworthy ; D. Isenberg ; A. Rahman ; M. Petri ; G S Alarc N ; C. Aranow ; M-A Dooley ; R. Rajan ; J-L Sénécal ; M. Zummer ; S. Manzi ; R. Ramsey-Goldman ; A E ClarkeSource :
- Annals of the Rheumatic Diseases [ 0003-4967 ] ; 2008-01.
English descriptors
- Teeft :
- America cohort entry, America sjogren syndrome, American college, Arthritis, Arthritis foundation, Aspirin, Autoimmune diseases, Azathioprine, Bladder cancers, Breast cancer, Calendar year, Cancer, Cancer cases, Cancer incidence, Cancer occurrence, Cancer risk, Carcinogenic risks, Categorical variables, Centre, Cervical, Cervical dysplasia, Chapel hill, Chemotherapy effects, Clinical characteristics, Clinical epidemiology, Clinical factors, Clinical immunology, Cohort, Cohort entry, Cohort studies, Cohort study, Confirmatory tests, Cumulative disease activity, Cumulative exposure, Cumulative exposures, Cyclophosphamide, Cyclophosphamide azathioprine methotrexate agents, Cyclophosphamide exposure, Cyclophosphamide exposures, Damage index, Damage item, Damage scores, Data collection, Disease activity, Drug exposures, Erythematosus, Exploratory analyses, Exposure categories, Glucocorticoids nsaids aspirin tobacco, Haematological, Haematological cancer, Haematological cancers, Haematological malignancies, Hazard ratio, Iarc monographs, Immunosuppressive, Immunosuppressive agents, Immunosuppressive drug, Immunosuppressive drug exposure, Immunosuppressive drug exposures, Immunosuppressive drugs, Immunosuppressive therapy, Immunosuppressive treatment, Index time, International agency, International cohort study, Intravenous, Intravenous cyclophosphamide, Invasive cancers, Investigator award, Johns hopkins university, Lung cancer, Lung cancers, Lupus, Lupus cohort, Lymphoma, Lymphoma risk, Malignancy, Malignancy risk, Mcgill university health centre, Medication, Medication exposures, Methotrexate, Nsaid, Organ damage, Other medication, Overall cancer risk, Parenteral exposures, Potential confounder, Power limitations, Primary analyses, Primary exposure, Report table, Research institute, Rheum, Rheumatic diseases, Rheumatoid arthritis, Rheumatol, Rheumatology, Rheumatology damage index, Second cancers, Separate analyses, Sicca symptoms, Sjogren, Sjogren syndrome, Study entry, Syndrome, Systematic overview, Systemic, Systemic lupus, Systemic lupus erythaematosus, Systemic lupus erythematosus, Time axis, Tobacco exposure, Tumour registries, White damage1 residence.
Abstract
Objective: To examine if, in systemic lupus erythaematosus (SLE), exposure to immunosuppressive therapy (cyclophosphamide, azathioprine, methotrexate) increases cancer risk. Methods: A case–cohort study was performed within a multi-site international SLE cohort; subjects were linked to regional tumour registries to determine cancer cases occurring after entry into the cohort. We calculated the hazard ratio (HR) for cancer after exposure to an immunosuppressive drug, in models that controlled for other medications (anti-malarial drugs, systemic glucocorticoids, non-steroidal anti-inflammatory drugs (NSAIDs), aspirin), smoking, age, sex, race/ethnicity, geographic location, calendar year, SLE duration, and lupus damage scores. In the primary analyses, exposures were treated categorically (ever/never) and as time-dependent. Results: Results are presented from 246 cancer cases and 538 controls without cancer. The adjusted HR for overall cancer risk after any immunosuppressive drug was 0.82 (95% CI 0.50–1.36). Age ⩾65, and the presence of non-malignancy damage were associated with overall cancer risk. For lung cancer (n = 35 cases), smoking was also a prominent risk factor. When looking at haematological cancers specifically (n = 46 cases), there was a suggestion of an increased risk after immunosuppressive drug exposures, particularly when these were lagged by a period of 5 years (adjusted HR 2.29, 95% CI 1.02–5.15). Conclusions: In our SLE sample, age ⩾65, damage, and tobacco exposure were associated with cancer risk. Though immunosuppressive therapy may not be the principal driving factor for overall cancer risk, it may contribute to an increased risk of haematological malignancies. Future studies are in progress to evaluate independent influence of medication exposures and disease activity on risk of malignancy.
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DOI: 10.1136/ard.2006.069039
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Joseph</name><affiliation><mods:affiliation>Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada</mods:affiliation></affiliation></author><author><name sortKey="Boivin, J F" sort="Boivin, J F" uniqKey="Boivin J" first="J-F" last="Boivin">J-F Boivin</name><affiliation><mods:affiliation>Division of Clinical Epidemiology, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada</mods:affiliation></affiliation></author><author><name sortKey="Gordon, C" sort="Gordon, C" uniqKey="Gordon C" first="C" last="Gordon">C. Gordon</name><affiliation><mods:affiliation>Division of Health Care & Outcomes Research, Toronto Western Research Institute, Toronto, Ontario, Canada</mods:affiliation></affiliation></author><author><name sortKey="Urowitz, M" sort="Urowitz, M" uniqKey="Urowitz M" first="M" last="Urowitz">M. 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Petri</name><affiliation><mods:affiliation>Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama, Birmingham, Alabama, USA</mods:affiliation></affiliation></author><author><name sortKey="Alarc N, G S" sort="Alarc N, G S" uniqKey="Alarc N G" first="G S" last="Alarc N">G S Alarc N</name><affiliation><mods:affiliation>Department of Medicine, Columbia University, New York, USA</mods:affiliation></affiliation></author><author><name sortKey="Aranow, C" sort="Aranow, C" uniqKey="Aranow C" first="C" last="Aranow">C. Aranow</name><affiliation><mods:affiliation>Department of Medicine, Thurston Arthritis Research Center, The University of North Carolina at Chapel Hill, North Carolina, USA</mods:affiliation></affiliation></author><author><name sortKey="Dooley, M A" sort="Dooley, M A" uniqKey="Dooley M" first="M-A" last="Dooley">M-A Dooley</name><affiliation><mods:affiliation>Department of Oncology, McGill University Health Centre, Montreal, Quebec, Canada</mods:affiliation></affiliation></author><author><name sortKey="Rajan, R" sort="Rajan, R" uniqKey="Rajan R" first="R" last="Rajan">R. Rajan</name><affiliation><mods:affiliation>Division of Rheumatology, Centre Hospitalier de l’Universite de Montreal, Department of Medicine, University of Montreal School of Medicine, Montreal, Quebec, Canada</mods:affiliation></affiliation></author><author><name sortKey="Senecal, J L" sort="Senecal, J L" uniqKey="Senecal J" first="J-L" last="Sénécal">J-L Sénécal</name><affiliation><mods:affiliation>Department of Rheumatology, Maisonneuve-Rosemont Hospital, Montreal, Quebec, Canada</mods:affiliation></affiliation></author><author><name sortKey="Zummer, M" sort="Zummer, M" uniqKey="Zummer M" first="M" last="Zummer">M. Zummer</name><affiliation><mods:affiliation>Division of Rheumatology and Clinical Immunology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA</mods:affiliation></affiliation></author><author><name sortKey="Manzi, S" sort="Manzi, S" uniqKey="Manzi S" first="S" last="Manzi">S. Manzi</name><affiliation><mods:affiliation>Division of Rheumatology, Northwestern University, Feinberg School of Medicine, Chicago, Illinois, USA</mods:affiliation></affiliation></author><author><name sortKey="Ramsey Goldman, R" sort="Ramsey Goldman, R" uniqKey="Ramsey Goldman R" first="R" last="Ramsey-Goldman">R. Ramsey-Goldman</name><affiliation><mods:affiliation>1 Division of Clinical Epidemiology, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada</mods:affiliation></affiliation><affiliation><mods:affiliation>2 Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada</mods:affiliation></affiliation><affiliation><mods:affiliation>3 Department of Rheumatology, University of Birmingham, UK</mods:affiliation></affiliation><affiliation><mods:affiliation>4 Division of Health Care & Outcomes Research, Toronto Western Research Institute, Toronto, Ontario, Canada</mods:affiliation></affiliation><affiliation><mods:affiliation>5 Division of Rheumatology, Department of Medicine, SUNY Health Science Center at Brooklyn, New York, USA</mods:affiliation></affiliation><affiliation><mods:affiliation>6 Department of Internal Medicine, Division of Rheumatology, Hanyang University College of Medicine and the Hospital of Rheumatic Diseases, Seoul, Korea</mods:affiliation></affiliation><affiliation><mods:affiliation>7 Division of Rheumatology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada</mods:affiliation></affiliation><affiliation><mods:affiliation>8 Centre for Rheumatology Research - Department of Medicine, University College London, UK</mods:affiliation></affiliation><affiliation><mods:affiliation>9 Division of Rheumatology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA</mods:affiliation></affiliation><affiliation><mods:affiliation>10 Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama, Birmingham, Alabama, USA</mods:affiliation></affiliation><affiliation><mods:affiliation>11 Department of Medicine, Columbia University, New York, USA</mods:affiliation></affiliation><affiliation><mods:affiliation>12 Department of Medicine, Thurston Arthritis Research Center, The University of North Carolina at Chapel Hill, North Carolina, USA</mods:affiliation></affiliation><affiliation><mods:affiliation>13 Department of Oncology, McGill University Health Centre, Montreal, Quebec, Canada</mods:affiliation></affiliation><affiliation><mods:affiliation>14 Division of Rheumatology, Centre Hospitalier de l’Universite de Montreal, Department of Medicine, University of Montreal School of Medicine, Montreal, Quebec, Canada</mods:affiliation></affiliation><affiliation><mods:affiliation>15 Department of Rheumatology, Maisonneuve-Rosemont Hospital, Montreal, Quebec, Canada</mods:affiliation></affiliation><affiliation><mods:affiliation>16 Division of Rheumatology and Clinical Immunology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA</mods:affiliation></affiliation><affiliation><mods:affiliation>17 Division of Rheumatology, Northwestern University, Feinberg School of Medicine, Chicago, Illinois, USA</mods:affiliation></affiliation></author><author><name sortKey="Clarke, A E" sort="Clarke, A E" uniqKey="Clarke A" first="A E" last="Clarke">A E Clarke</name><affiliation><mods:affiliation>Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada</mods:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:A4ED4E047016C31087BDE29E164614EA04E5C400</idno><date when="2008" year="2008">2008</date><idno type="doi">10.1136/ard.2006.069039</idno><idno type="url">https://api.istex.fr/ark:/67375/NVC-KQHFPBGL-7/fulltext.pdf</idno><idno type="wicri:Area/Istex/Corpus">001C00</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">001C00</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">The relationship between cancer and medication exposures in systemic lupus erythaematosus: a case–cohort study</title><author><name sortKey="Bernatsky, S" sort="Bernatsky, S" uniqKey="Bernatsky S" first="S" last="Bernatsky">S. Bernatsky</name><affiliation><mods:affiliation>Division of Clinical Epidemiology, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada</mods:affiliation></affiliation></author><author><name sortKey="Joseph, L" sort="Joseph, L" uniqKey="Joseph L" first="L" last="Joseph">L. Joseph</name><affiliation><mods:affiliation>Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada</mods:affiliation></affiliation></author><author><name sortKey="Boivin, J F" sort="Boivin, J F" uniqKey="Boivin J" first="J-F" last="Boivin">J-F Boivin</name><affiliation><mods:affiliation>Division of Clinical Epidemiology, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada</mods:affiliation></affiliation></author><author><name sortKey="Gordon, C" sort="Gordon, C" uniqKey="Gordon C" first="C" last="Gordon">C. Gordon</name><affiliation><mods:affiliation>Division of Health Care & Outcomes Research, Toronto Western Research Institute, Toronto, Ontario, Canada</mods:affiliation></affiliation></author><author><name sortKey="Urowitz, M" sort="Urowitz, M" uniqKey="Urowitz M" first="M" last="Urowitz">M. Urowitz</name><affiliation><mods:affiliation>Division of Rheumatology, Department of Medicine, SUNY Health Science Center at Brooklyn, New York, USA</mods:affiliation></affiliation></author><author><name sortKey="Gladman, D" sort="Gladman, D" uniqKey="Gladman D" first="D" last="Gladman">D. Gladman</name><affiliation><mods:affiliation>Division of Rheumatology, Department of Medicine, SUNY Health Science Center at Brooklyn, New York, USA</mods:affiliation></affiliation></author><author><name sortKey="Fortin, P R" sort="Fortin, P R" uniqKey="Fortin P" first="P R" last="Fortin">P R Fortin</name><affiliation><mods:affiliation>Division of Rheumatology, Department of Medicine, SUNY Health Science Center at Brooklyn, New York, USA</mods:affiliation></affiliation></author><author><name sortKey="Ginzler, E" sort="Ginzler, E" uniqKey="Ginzler E" first="E" last="Ginzler">E. Ginzler</name><affiliation><mods:affiliation>Department of Internal Medicine, Division of Rheumatology, Hanyang University College of Medicine and the Hospital of Rheumatic Diseases, Seoul, Korea</mods:affiliation></affiliation></author><author><name sortKey="Bae, S C" sort="Bae, S C" uniqKey="Bae S" first="S-C" last="Bae">S-C Bae</name><affiliation><mods:affiliation>Division of Rheumatology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada</mods:affiliation></affiliation></author><author><name sortKey="Barr, S" sort="Barr, S" uniqKey="Barr S" first="S" last="Barr">S. Barr</name><affiliation><mods:affiliation>Centre for Rheumatology Research - Department of Medicine, University College London, UK</mods:affiliation></affiliation></author><author><name sortKey="Edworthy, S" sort="Edworthy, S" uniqKey="Edworthy S" first="S" last="Edworthy">S. Edworthy</name><affiliation><mods:affiliation>Centre for Rheumatology Research - Department of Medicine, University College London, UK</mods:affiliation></affiliation></author><author><name sortKey="Isenberg, D" sort="Isenberg, D" uniqKey="Isenberg D" first="D" last="Isenberg">D. Isenberg</name><affiliation><mods:affiliation>Division of Rheumatology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA</mods:affiliation></affiliation></author><author><name sortKey="Rahman, A" sort="Rahman, A" uniqKey="Rahman A" first="A" last="Rahman">A. Rahman</name><affiliation><mods:affiliation>Division of Rheumatology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA</mods:affiliation></affiliation></author><author><name sortKey="Petri, M" sort="Petri, M" uniqKey="Petri M" first="M" last="Petri">M. Petri</name><affiliation><mods:affiliation>Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama, Birmingham, Alabama, USA</mods:affiliation></affiliation></author><author><name sortKey="Alarc N, G S" sort="Alarc N, G S" uniqKey="Alarc N G" first="G S" last="Alarc N">G S Alarc N</name><affiliation><mods:affiliation>Department of Medicine, Columbia University, New York, USA</mods:affiliation></affiliation></author><author><name sortKey="Aranow, C" sort="Aranow, C" uniqKey="Aranow C" first="C" last="Aranow">C. Aranow</name><affiliation><mods:affiliation>Department of Medicine, Thurston Arthritis Research Center, The University of North Carolina at Chapel Hill, North Carolina, USA</mods:affiliation></affiliation></author><author><name sortKey="Dooley, M A" sort="Dooley, M A" uniqKey="Dooley M" first="M-A" last="Dooley">M-A Dooley</name><affiliation><mods:affiliation>Department of Oncology, McGill University Health Centre, Montreal, Quebec, Canada</mods:affiliation></affiliation></author><author><name sortKey="Rajan, R" sort="Rajan, R" uniqKey="Rajan R" first="R" last="Rajan">R. Rajan</name><affiliation><mods:affiliation>Division of Rheumatology, Centre Hospitalier de l’Universite de Montreal, Department of Medicine, University of Montreal School of Medicine, Montreal, Quebec, Canada</mods:affiliation></affiliation></author><author><name sortKey="Senecal, J L" sort="Senecal, J L" uniqKey="Senecal J" first="J-L" last="Sénécal">J-L Sénécal</name><affiliation><mods:affiliation>Department of Rheumatology, Maisonneuve-Rosemont Hospital, Montreal, Quebec, Canada</mods:affiliation></affiliation></author><author><name sortKey="Zummer, M" sort="Zummer, M" uniqKey="Zummer M" first="M" last="Zummer">M. Zummer</name><affiliation><mods:affiliation>Division of Rheumatology and Clinical Immunology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA</mods:affiliation></affiliation></author><author><name sortKey="Manzi, S" sort="Manzi, S" uniqKey="Manzi S" first="S" last="Manzi">S. Manzi</name><affiliation><mods:affiliation>Division of Rheumatology, Northwestern University, Feinberg School of Medicine, Chicago, Illinois, USA</mods:affiliation></affiliation></author><author><name sortKey="Ramsey Goldman, R" sort="Ramsey Goldman, R" uniqKey="Ramsey Goldman R" first="R" last="Ramsey-Goldman">R. Ramsey-Goldman</name><affiliation><mods:affiliation>1 Division of Clinical Epidemiology, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada</mods:affiliation></affiliation><affiliation><mods:affiliation>2 Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada</mods:affiliation></affiliation><affiliation><mods:affiliation>3 Department of Rheumatology, University of Birmingham, UK</mods:affiliation></affiliation><affiliation><mods:affiliation>4 Division of Health Care & Outcomes Research, Toronto Western Research Institute, Toronto, Ontario, Canada</mods:affiliation></affiliation><affiliation><mods:affiliation>5 Division of Rheumatology, Department of Medicine, SUNY Health Science Center at Brooklyn, New York, USA</mods:affiliation></affiliation><affiliation><mods:affiliation>6 Department of Internal Medicine, Division of Rheumatology, Hanyang University College of Medicine and the Hospital of Rheumatic Diseases, Seoul, Korea</mods:affiliation></affiliation><affiliation><mods:affiliation>7 Division of Rheumatology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada</mods:affiliation></affiliation><affiliation><mods:affiliation>8 Centre for Rheumatology Research - Department of Medicine, University College London, UK</mods:affiliation></affiliation><affiliation><mods:affiliation>9 Division of Rheumatology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA</mods:affiliation></affiliation><affiliation><mods:affiliation>10 Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama, Birmingham, Alabama, USA</mods:affiliation></affiliation><affiliation><mods:affiliation>11 Department of Medicine, Columbia University, New York, USA</mods:affiliation></affiliation><affiliation><mods:affiliation>12 Department of Medicine, Thurston Arthritis Research Center, The University of North Carolina at Chapel Hill, North Carolina, USA</mods:affiliation></affiliation><affiliation><mods:affiliation>13 Department of Oncology, McGill University Health Centre, Montreal, Quebec, Canada</mods:affiliation></affiliation><affiliation><mods:affiliation>14 Division of Rheumatology, Centre Hospitalier de l’Universite de Montreal, Department of Medicine, University of Montreal School of Medicine, Montreal, Quebec, Canada</mods:affiliation></affiliation><affiliation><mods:affiliation>15 Department of Rheumatology, Maisonneuve-Rosemont Hospital, Montreal, Quebec, Canada</mods:affiliation></affiliation><affiliation><mods:affiliation>16 Division of Rheumatology and Clinical Immunology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA</mods:affiliation></affiliation><affiliation><mods:affiliation>17 Division of Rheumatology, Northwestern University, Feinberg School of Medicine, Chicago, Illinois, USA</mods:affiliation></affiliation></author><author><name sortKey="Clarke, A E" sort="Clarke, A E" uniqKey="Clarke A" first="A E" last="Clarke">A E Clarke</name><affiliation><mods:affiliation>Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Annals of the Rheumatic Diseases</title><title level="j" type="abbrev">Ann Rheum Dis</title><idno type="ISSN">0003-4967</idno><idno type="eISSN">1468-2060</idno><imprint><publisher>BMJ Publishing Group Ltd and European League Against Rheumatism</publisher><date type="published" when="2008-01">2008-01</date><biblScope unit="volume">67</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="74">74</biblScope></imprint><idno type="ISSN">0003-4967</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0003-4967</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="Teeft" xml:lang="en"><term>America cohort entry</term><term>America sjogren 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azathioprine methotrexate agents</term><term>Cyclophosphamide exposure</term><term>Cyclophosphamide exposures</term><term>Damage index</term><term>Damage item</term><term>Damage scores</term><term>Data collection</term><term>Disease activity</term><term>Drug exposures</term><term>Erythematosus</term><term>Exploratory analyses</term><term>Exposure categories</term><term>Glucocorticoids nsaids aspirin tobacco</term><term>Haematological</term><term>Haematological cancer</term><term>Haematological cancers</term><term>Haematological malignancies</term><term>Hazard ratio</term><term>Iarc monographs</term><term>Immunosuppressive</term><term>Immunosuppressive agents</term><term>Immunosuppressive drug</term><term>Immunosuppressive drug exposure</term><term>Immunosuppressive drug exposures</term><term>Immunosuppressive drugs</term><term>Immunosuppressive therapy</term><term>Immunosuppressive treatment</term><term>Index time</term><term>International agency</term><term>International cohort study</term><term>Intravenous</term><term>Intravenous cyclophosphamide</term><term>Invasive cancers</term><term>Investigator award</term><term>Johns hopkins university</term><term>Lung cancer</term><term>Lung cancers</term><term>Lupus</term><term>Lupus cohort</term><term>Lymphoma</term><term>Lymphoma risk</term><term>Malignancy</term><term>Malignancy risk</term><term>Mcgill university health centre</term><term>Medication</term><term>Medication exposures</term><term>Methotrexate</term><term>Nsaid</term><term>Organ damage</term><term>Other medication</term><term>Overall cancer risk</term><term>Parenteral exposures</term><term>Potential confounder</term><term>Power limitations</term><term>Primary analyses</term><term>Primary exposure</term><term>Report table</term><term>Research institute</term><term>Rheum</term><term>Rheumatic diseases</term><term>Rheumatoid arthritis</term><term>Rheumatol</term><term>Rheumatology</term><term>Rheumatology damage index</term><term>Second cancers</term><term>Separate analyses</term><term>Sicca symptoms</term><term>Sjogren</term><term>Sjogren syndrome</term><term>Study entry</term><term>Syndrome</term><term>Systematic overview</term><term>Systemic</term><term>Systemic lupus</term><term>Systemic lupus erythaematosus</term><term>Systemic lupus erythematosus</term><term>Time axis</term><term>Tobacco exposure</term><term>Tumour registries</term><term>White damage1 residence</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract">Objective: To examine if, in systemic lupus erythaematosus (SLE), exposure to immunosuppressive therapy (cyclophosphamide, azathioprine, methotrexate) increases cancer risk. Methods: A case–cohort study was performed within a multi-site international SLE cohort; subjects were linked to regional tumour registries to determine cancer cases occurring after entry into the cohort. We calculated the hazard ratio (HR) for cancer after exposure to an immunosuppressive drug, in models that controlled for other medications (anti-malarial drugs, systemic glucocorticoids, non-steroidal anti-inflammatory drugs (NSAIDs), aspirin), smoking, age, sex, race/ethnicity, geographic location, calendar year, SLE duration, and lupus damage scores. In the primary analyses, exposures were treated categorically (ever/never) and as time-dependent. Results: Results are presented from 246 cancer cases and 538 controls without cancer. The adjusted HR for overall cancer risk after any immunosuppressive drug was 0.82 (95% CI 0.50–1.36). Age ⩾65, and the presence of non-malignancy damage were associated with overall cancer risk. For lung cancer (n = 35 cases), smoking was also a prominent risk factor. When looking at haematological cancers specifically (n = 46 cases), there was a suggestion of an increased risk after immunosuppressive drug exposures, particularly when these were lagged by a period of 5 years (adjusted HR 2.29, 95% CI 1.02–5.15). Conclusions: In our SLE sample, age ⩾65, damage, and tobacco exposure were associated with cancer risk. Though immunosuppressive therapy may not be the principal driving factor for overall cancer risk, it may contribute to an increased risk of haematological malignancies. Future studies are in progress to evaluate independent influence of medication exposures and disease activity on risk of malignancy.</div></front></TEI><istex><corpusName>bmj</corpusName><keywords><teeft><json:string>lupus</json:string><json:string>immunosuppressive</json:string><json:string>cohort</json:string><json:string>cyclophosphamide</json:string><json:string>azathioprine</json:string><json:string>haematological</json:string><json:string>rheumatology</json:string><json:string>erythematosus</json:string><json:string>cancer risk</json:string><json:string>systemic lupus erythematosus</json:string><json:string>methotrexate</json:string><json:string>nsaid</json:string><json:string>malignancy</json:string><json:string>sjogren</json:string><json:string>cancer cases</json:string><json:string>lung cancer</json:string><json:string>disease activity</json:string><json:string>rheum</json:string><json:string>immunosuppressive 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cancers</json:string><json:string>mcgill university health centre</json:string><json:string>american college</json:string><json:string>syndrome</json:string><json:string>cancer</json:string><json:string>time axis</json:string><json:string>international cohort study</json:string><json:string>categorical variables</json:string><json:string>cohort studies</json:string><json:string>immunosuppressive drug exposures</json:string><json:string>report table</json:string><json:string>clinical factors</json:string><json:string>study entry</json:string><json:string>other medication</json:string><json:string>immunosuppressive treatment</json:string><json:string>johns hopkins university</json:string><json:string>cyclophosphamide exposures</json:string><json:string>cumulative exposure</json:string><json:string>exposure categories</json:string><json:string>research institute</json:string><json:string>separate analyses</json:string><json:string>america cohort entry</json:string><json:string>cyclophosphamide azathioprine methotrexate agents</json:string><json:string>america sjogren syndrome</json:string><json:string>white damage1 residence</json:string><json:string>parenteral exposures</json:string><json:string>clinical immunology</json:string><json:string>autoimmune diseases</json:string><json:string>potential confounder</json:string><json:string>cumulative disease activity</json:string><json:string>power limitations</json:string><json:string>damage item</json:string><json:string>bladder cancers</json:string><json:string>intravenous cyclophosphamide</json:string><json:string>clinical epidemiology</json:string><json:string>chapel hill</json:string><json:string>tumour registries</json:string><json:string>exploratory analyses</json:string><json:string>immunosuppressive drug exposure</json:string><json:string>second cancers</json:string><json:string>lymphoma risk</json:string><json:string>data collection</json:string><json:string>investigator award</json:string><json:string>arthritis foundation</json:string><json:string>invasive cancers</json:string><json:string>lupus cohort</json:string><json:string>cancer incidence</json:string><json:string>rheumatic diseases</json:string><json:string>systematic overview</json:string><json:string>iarc monographs</json:string><json:string>carcinogenic risks</json:string><json:string>chemotherapy effects</json:string><json:string>aspirin</json:string></teeft></keywords><author><json:item><name>S Bernatsky</name><affiliations><json:string>Division of Clinical Epidemiology, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada</json:string></affiliations></json:item><json:item><name>L Joseph</name><affiliations><json:string>Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada</json:string></affiliations></json:item><json:item><name>J-F Boivin</name><affiliations><json:string>Division of Clinical Epidemiology, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada</json:string></affiliations></json:item><json:item><name>C Gordon</name><affiliations><json:string>Division of Health Care & Outcomes Research, Toronto Western Research Institute, Toronto, Ontario, Canada</json:string></affiliations></json:item><json:item><name>M Urowitz</name><affiliations><json:string>Division of Rheumatology, Department of Medicine, SUNY Health Science Center at Brooklyn, New York, USA</json:string></affiliations></json:item><json:item><name>D Gladman</name><affiliations><json:string>Division of Rheumatology, Department of Medicine, SUNY Health Science Center at Brooklyn, New York, USA</json:string></affiliations></json:item><json:item><name>P R Fortin</name><affiliations><json:string>Division of Rheumatology, Department of Medicine, SUNY Health Science Center at Brooklyn, New York, USA</json:string></affiliations></json:item><json:item><name>E Ginzler</name><affiliations><json:string>Department of Internal Medicine, Division of Rheumatology, Hanyang University College of Medicine and the Hospital of Rheumatic Diseases, Seoul, Korea</json:string></affiliations></json:item><json:item><name>S-C Bae</name><affiliations><json:string>Division of Rheumatology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada</json:string></affiliations></json:item><json:item><name>S Barr</name><affiliations><json:string>Centre for Rheumatology Research - Department of Medicine, University College London, UK</json:string></affiliations></json:item><json:item><name>S Edworthy</name><affiliations><json:string>Centre for Rheumatology Research - Department of Medicine, University College London, UK</json:string></affiliations></json:item><json:item><name>D Isenberg</name><affiliations><json:string>Division of Rheumatology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA</json:string></affiliations></json:item><json:item><name>A Rahman</name><affiliations><json:string>Division of Rheumatology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA</json:string></affiliations></json:item><json:item><name>M Petri</name><affiliations><json:string>Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama, Birmingham, Alabama, USA</json:string></affiliations></json:item><json:item><name>G S Alarcón</name><affiliations><json:string>Department of Medicine, Columbia University, New York, USA</json:string></affiliations></json:item><json:item><name>C Aranow</name><affiliations><json:string>Department of Medicine, Thurston Arthritis Research Center, The University of North Carolina at Chapel Hill, North Carolina, USA</json:string></affiliations></json:item><json:item><name>M-A Dooley</name><affiliations><json:string>Department of Oncology, McGill University Health Centre, Montreal, Quebec, Canada</json:string></affiliations></json:item><json:item><name>R Rajan</name><affiliations><json:string>Division of Rheumatology, Centre Hospitalier de l’Universite de Montreal, Department of Medicine, University of Montreal School of Medicine, Montreal, Quebec, Canada</json:string></affiliations></json:item><json:item><name>J-L Sénécal</name><affiliations><json:string>Department of Rheumatology, Maisonneuve-Rosemont Hospital, Montreal, Quebec, Canada</json:string></affiliations></json:item><json:item><name>M Zummer</name><affiliations><json:string>Division of Rheumatology and Clinical Immunology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA</json:string></affiliations></json:item><json:item><name>S Manzi</name><affiliations><json:string>Division of Rheumatology, Northwestern University, Feinberg School of Medicine, Chicago, Illinois, USA</json:string></affiliations></json:item><json:item><name>R Ramsey-Goldman</name><affiliations><json:string>1 Division of Clinical Epidemiology, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada</json:string><json:string>2 Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada</json:string><json:string>3 Department of Rheumatology, University of Birmingham, UK</json:string><json:string>4 Division of Health Care & Outcomes Research, Toronto Western Research Institute, Toronto, Ontario, Canada</json:string><json:string>5 Division of Rheumatology, Department of Medicine, SUNY Health Science Center at Brooklyn, New York, USA</json:string><json:string>6 Department of Internal Medicine, Division of Rheumatology, Hanyang University College of Medicine and the Hospital of Rheumatic Diseases, Seoul, Korea</json:string><json:string>7 Division of Rheumatology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada</json:string><json:string>8 Centre for Rheumatology Research - Department of Medicine, University College London, UK</json:string><json:string>9 Division of Rheumatology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA</json:string><json:string>10 Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama, Birmingham, Alabama, USA</json:string><json:string>11 Department of Medicine, Columbia University, New York, USA</json:string><json:string>12 Department of Medicine, Thurston Arthritis Research Center, The University of North Carolina at Chapel Hill, North Carolina, USA</json:string><json:string>13 Department of Oncology, McGill University Health Centre, Montreal, Quebec, Canada</json:string><json:string>14 Division of Rheumatology, Centre Hospitalier de l’Universite de Montreal, Department of Medicine, University of Montreal School of Medicine, Montreal, Quebec, Canada</json:string><json:string>15 Department of Rheumatology, Maisonneuve-Rosemont Hospital, Montreal, Quebec, Canada</json:string><json:string>16 Division of Rheumatology and Clinical Immunology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA</json:string><json:string>17 Division of Rheumatology, Northwestern University, Feinberg School of Medicine, Chicago, Illinois, USA</json:string></affiliations></json:item><json:item><name>A E Clarke</name><affiliations><json:string>Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada</json:string></affiliations></json:item></author><articleId><json:string>ar69039</json:string></articleId><arkIstex>ark:/67375/NVC-KQHFPBGL-7</arkIstex><language><json:string>eng</json:string></language><originalGenre><json:string>research-article</json:string></originalGenre><abstract>Objective: To examine if, in systemic lupus erythaematosus (SLE), exposure to immunosuppressive therapy (cyclophosphamide, azathioprine, methotrexate) increases cancer risk. Methods: A case–cohort study was performed within a multi-site international SLE cohort; subjects were linked to regional tumour registries to determine cancer cases occurring after entry into the cohort. We calculated the hazard ratio (HR) for cancer after exposure to an immunosuppressive drug, in models that controlled for other medications (anti-malarial drugs, systemic glucocorticoids, non-steroidal anti-inflammatory drugs (NSAIDs), aspirin), smoking, age, sex, race/ethnicity, geographic location, calendar year, SLE duration, and lupus damage scores. In the primary analyses, exposures were treated categorically (ever/never) and as time-dependent. Results: Results are presented from 246 cancer cases and 538 controls without cancer. The adjusted HR for overall cancer risk after any immunosuppressive drug was 0.82 (95% CI 0.50–1.36). Age ⩾65, and the presence of non-malignancy damage were associated with overall cancer risk. For lung cancer (n = 35 cases), smoking was also a prominent risk factor. When looking at haematological cancers specifically (n = 46 cases), there was a suggestion of an increased risk after immunosuppressive drug exposures, particularly when these were lagged by a period of 5 years (adjusted HR 2.29, 95% CI 1.02–5.15). Conclusions: In our SLE sample, age ⩾65, damage, and tobacco exposure were associated with cancer risk. Though immunosuppressive therapy may not be the principal driving factor for overall cancer risk, it may contribute to an increased risk of haematological malignancies. Future studies are in progress to evaluate independent influence of medication exposures and disease activity on risk of malignancy.</abstract><qualityIndicators><score>10</score><pdfWordCount>5051</pdfWordCount><pdfCharCount>35913</pdfCharCount><pdfVersion>1.2</pdfVersion><pdfPageCount>6</pdfPageCount><pdfPageSize>595.276 x 793.701 pts</pdfPageSize><refBibsNative>true</refBibsNative><abstractWordCount>255</abstractWordCount><abstractCharCount>1842</abstractCharCount><keywordCount>0</keywordCount></qualityIndicators><title>The relationship between cancer and medication exposures in systemic lupus erythaematosus: a case–cohort study</title><pmid><json:string>17545189</json:string></pmid><genre><json:string>research-article</json:string></genre><host><title>Annals of the Rheumatic Diseases</title><language><json:string>unknown</json:string></language><issn><json:string>0003-4967</json:string></issn><eissn><json:string>1468-2060</json:string></eissn><publisherId><json:string>ard</json:string></publisherId><volume>67</volume><issue>1</issue><pages><first>74</first></pages><genre><json:string>journal</json:string></genre><subject><json:item><value>Immunology (including allergy)</value></json:item><json:item><value>Biological agents</value></json:item><json:item><value>Drugs: musculoskeletal and joint diseases</value></json:item><json:item><value>Epidemiology</value></json:item></subject></host><namedEntities><unitex><date><json:string>2007-06-01</json:string><json:string>1990</json:string></date><geogName></geogName><orgName><json:string>University of Pittsburgh, Pittsburgh</json:string><json:string>Outcomes Research, Toronto Western Research Institute, Toronto, Ontario, Canada</json:string><json:string>Division of Health Care</json:string><json:string>Rheumatology Research Department of Medicine, University College London, UK</json:string><json:string>Northwestern University</json:string><json:string>University of Alabama</json:string><json:string>Department of Internal Medicine, Division of Rheumatology, Hanyang University College of Medicine</json:string><json:string>Arthritis Foundation, Clinical Science Grant, Arthritis Foundation Greater Chicago Chapter NIH RO</json:string><json:string>FRSQ National Scholar Award</json:string><json:string>Hospital, Montreal, Quebec, Canada</json:string><json:string>Research Institute</json:string><json:string>Pennsylvania Department of Health</json:string><json:string>Division of Clinical Immunology</json:string><json:string>Division of Clinical Epidemiology</json:string><json:string>Systemic Lupus International Collaborating Clinics</json:string><json:string>Department of Epidemiology, Biostatistics and Occupational Health</json:string><json:string>Department of Medicine, Thurston Arthritis Research 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McKinnon</json:string><json:string>Gina Banks</json:string><json:string>The</json:string><json:string>Extended</json:string><json:string>Stephanie Heaton</json:string><json:string>Deva Situnayake</json:string><json:string>Veronica Toescu</json:string><json:string>Martha Sanchez</json:string><json:string>Whitney Steber</json:string><json:string>Dr Simon</json:string><json:string>Sasha Bernatsky</json:string></persName><placeName><json:string>Calgary</json:string><json:string>Birmingham</json:string><json:string>Korea</json:string><json:string>UK</json:string><json:string>Pittsburgh</json:string><json:string>Canada</json:string><json:string>New York City</json:string><json:string>Toronto</json:string><json:string>Europe</json:string><json:string>America</json:string><json:string>Baltimore</json:string><json:string>Chicago</json:string><json:string>York</json:string><json:string>Quebec</json:string></placeName><ref_url></ref_url><ref_bibl><json:string>Asten et al</json:string><json:string>Baecklund et al</json:string><json:string>Baker et al</json:string></ref_bibl><bibl></bibl></unitex></namedEntities><ark><json:string>ark:/67375/NVC-KQHFPBGL-7</json:string></ark><categories><wos><json:string>1 - science</json:string><json:string>2 - rheumatology</json:string></wos><scienceMetrix><json:string>1 - health sciences</json:string><json:string>2 - clinical medicine</json:string><json:string>3 - arthritis & rheumatology</json:string></scienceMetrix><scopus><json:string>1 - Life Sciences</json:string><json:string>2 - Biochemistry, Genetics and Molecular Biology</json:string><json:string>3 - General Biochemistry, Genetics and Molecular Biology</json:string><json:string>1 - Life Sciences</json:string><json:string>2 - Immunology and Microbiology</json:string><json:string>3 - Immunology</json:string><json:string>1 - Health Sciences</json:string><json:string>2 - Medicine</json:string><json:string>3 - Immunology and Allergy</json:string><json:string>1 - 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level="a" type="main" xml:lang="en">The relationship between cancer and medication exposures in systemic lupus erythaematosus: a case–cohort study</title><author xml:id="author-0000"><persName><forename type="first">S</forename><surname>Bernatsky</surname></persName><affiliation>Division of Clinical Epidemiology, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada</affiliation></author><author xml:id="author-0001"><persName><forename type="first">L</forename><surname>Joseph</surname></persName><affiliation>Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada</affiliation></author><author xml:id="author-0002"><persName><forename type="first">J-F</forename><surname>Boivin</surname></persName><affiliation>Division of Clinical Epidemiology, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada</affiliation></author><author xml:id="author-0003"><persName><forename type="first">C</forename><surname>Gordon</surname></persName><affiliation>Division of Health Care & Outcomes Research, Toronto Western Research Institute, Toronto, Ontario, Canada</affiliation></author><author xml:id="author-0004"><persName><forename type="first">M</forename><surname>Urowitz</surname></persName><affiliation>Division of Rheumatology, Department of Medicine, SUNY Health Science Center at Brooklyn, New York, USA</affiliation></author><author xml:id="author-0005"><persName><forename type="first">D</forename><surname>Gladman</surname></persName><affiliation>Division of Rheumatology, Department of Medicine, SUNY Health Science Center at Brooklyn, New York, USA</affiliation></author><author xml:id="author-0006"><persName><forename type="first">P R</forename><surname>Fortin</surname></persName><affiliation>Division of Rheumatology, Department of Medicine, SUNY Health Science Center at Brooklyn, New York, USA</affiliation></author><author xml:id="author-0007"><persName><forename type="first">E</forename><surname>Ginzler</surname></persName><affiliation>Department of Internal Medicine, Division of Rheumatology, Hanyang University College of Medicine and the Hospital of Rheumatic Diseases, Seoul, Korea</affiliation></author><author xml:id="author-0008"><persName><forename type="first">S-C</forename><surname>Bae</surname></persName><affiliation>Division of Rheumatology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada</affiliation></author><author xml:id="author-0009"><persName><forename type="first">S</forename><surname>Barr</surname></persName><affiliation>Centre for Rheumatology Research - Department of Medicine, University College London, UK</affiliation></author><author xml:id="author-0010"><persName><forename type="first">S</forename><surname>Edworthy</surname></persName><affiliation>Centre for Rheumatology Research - Department of Medicine, University College London, UK</affiliation></author><author xml:id="author-0011"><persName><forename type="first">D</forename><surname>Isenberg</surname></persName><affiliation>Division of Rheumatology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA</affiliation></author><author xml:id="author-0012"><persName><forename type="first">A</forename><surname>Rahman</surname></persName><affiliation>Division of Rheumatology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA</affiliation></author><author xml:id="author-0013"><persName><forename type="first">M</forename><surname>Petri</surname></persName><affiliation>Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama, Birmingham, Alabama, USA</affiliation></author><author xml:id="author-0014"><persName><forename type="first">G S</forename><surname>Alarcón</surname></persName><affiliation>Department of Medicine, Columbia University, New York, USA</affiliation></author><author xml:id="author-0015"><persName><forename type="first">C</forename><surname>Aranow</surname></persName><affiliation>Department of Medicine, Thurston Arthritis Research Center, The University of North Carolina at Chapel Hill, North Carolina, USA</affiliation></author><author xml:id="author-0016"><persName><forename type="first">M-A</forename><surname>Dooley</surname></persName><affiliation>Department of Oncology, McGill University Health Centre, Montreal, Quebec, Canada</affiliation></author><author xml:id="author-0017"><persName><forename type="first">R</forename><surname>Rajan</surname></persName><affiliation>Division of Rheumatology, Centre Hospitalier de l’Universite de Montreal, Department of Medicine, University of Montreal School of Medicine, Montreal, Quebec, Canada</affiliation></author><author xml:id="author-0018"><persName><forename type="first">J-L</forename><surname>Sénécal</surname></persName><affiliation>Department of Rheumatology, Maisonneuve-Rosemont Hospital, Montreal, Quebec, Canada</affiliation></author><author xml:id="author-0019"><persName><forename type="first">M</forename><surname>Zummer</surname></persName><affiliation>Division of Rheumatology and Clinical Immunology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA</affiliation></author><author xml:id="author-0020"><persName><forename type="first">S</forename><surname>Manzi</surname></persName><affiliation>Division of Rheumatology, Northwestern University, Feinberg School of Medicine, Chicago, Illinois, USA</affiliation></author><author xml:id="author-0021"><persName><forename type="first">R</forename><surname>Ramsey-Goldman</surname></persName><affiliation>1 Division of Clinical Epidemiology, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada</affiliation><affiliation>2 Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada</affiliation><affiliation>3 Department of Rheumatology, University of Birmingham, UK</affiliation><affiliation>4 Division of Health Care & Outcomes Research, Toronto Western Research Institute, Toronto, Ontario, Canada</affiliation><affiliation>5 Division of Rheumatology, Department of Medicine, SUNY Health Science Center at Brooklyn, New York, USA</affiliation><affiliation>6 Department of Internal Medicine, Division of Rheumatology, Hanyang University College of Medicine and the Hospital of Rheumatic Diseases, Seoul, Korea</affiliation><affiliation>7 Division of Rheumatology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada</affiliation><affiliation>8 Centre for Rheumatology Research - Department of Medicine, University College London, UK</affiliation><affiliation>9 Division of Rheumatology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA</affiliation><affiliation>10 Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama, Birmingham, Alabama, USA</affiliation><affiliation>11 Department of Medicine, Columbia University, New York, USA</affiliation><affiliation>12 Department of Medicine, Thurston Arthritis Research Center, The University of North Carolina at Chapel Hill, North Carolina, USA</affiliation><affiliation>13 Department of Oncology, McGill University Health Centre, Montreal, Quebec, Canada</affiliation><affiliation>14 Division of Rheumatology, Centre Hospitalier de l’Universite de Montreal, Department of Medicine, University of Montreal School of Medicine, Montreal, Quebec, Canada</affiliation><affiliation>15 Department of Rheumatology, Maisonneuve-Rosemont Hospital, Montreal, Quebec, Canada</affiliation><affiliation>16 Division of Rheumatology and Clinical Immunology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA</affiliation><affiliation>17 Division of Rheumatology, Northwestern University, Feinberg School of Medicine, Chicago, Illinois, USA</affiliation></author><author xml:id="author-0022"><persName><forename type="first">A E</forename><surname>Clarke</surname></persName><affiliation>Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada</affiliation></author><idno type="istex">A4ED4E047016C31087BDE29E164614EA04E5C400</idno><idno type="ark">ark:/67375/NVC-KQHFPBGL-7</idno><idno type="DOI">10.1136/ard.2006.069039</idno><idno type="href">annrheumdis-67-74.pdf</idno><idno type="article-id">ar69039</idno><idno type="PMID">17545189</idno><idno type="local">annrheumdis;67/1/74</idno></analytic><monogr><title level="j">Annals of the Rheumatic Diseases</title><title level="j" type="abbrev">Ann Rheum Dis</title><idno type="pISSN">0003-4967</idno><idno type="eISSN">1468-2060</idno><idno type="publisher-id">ard</idno><idno type="PublisherID-hwp">annrheumdis</idno><idno type="PublisherID-nlm-ta">Ann Rheum Dis</idno><imprint><publisher>BMJ Publishing Group Ltd and European League Against Rheumatism</publisher><date type="published" when="2008-01"></date><biblScope unit="volume">67</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="74">74</biblScope></imprint></monogr></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2007-06-01</date></creation><langUsage><language ident="en">en</language></langUsage><abstract><p>Objective: To examine if, in systemic lupus erythaematosus (SLE), exposure to immunosuppressive therapy (cyclophosphamide, azathioprine, methotrexate) increases cancer risk. Methods: A case–cohort study was performed within a multi-site international SLE cohort; subjects were linked to regional tumour registries to determine cancer cases occurring after entry into the cohort. We calculated the hazard ratio (HR) for cancer after exposure to an immunosuppressive drug, in models that controlled for other medications (anti-malarial drugs, systemic glucocorticoids, non-steroidal anti-inflammatory drugs (NSAIDs), aspirin), smoking, age, sex, race/ethnicity, geographic location, calendar year, SLE duration, and lupus damage scores. In the primary analyses, exposures were treated categorically (ever/never) and as time-dependent. Results: Results are presented from 246 cancer cases and 538 controls without cancer. The adjusted HR for overall cancer risk after any immunosuppressive drug was 0.82 (95% CI 0.50–1.36). Age ⩾65, and the presence of non-malignancy damage were associated with overall cancer risk. For lung cancer (n = 35 cases), smoking was also a prominent risk factor. When looking at haematological cancers specifically (n = 46 cases), there was a suggestion of an increased risk after immunosuppressive drug exposures, particularly when these were lagged by a period of 5 years (adjusted HR 2.29, 95% CI 1.02–5.15). Conclusions: In our SLE sample, age ⩾65, damage, and tobacco exposure were associated with cancer risk. Though immunosuppressive therapy may not be the principal driving factor for overall cancer risk, it may contribute to an increased risk of haematological malignancies. Future studies are in progress to evaluate independent influence of medication exposures and disease activity on risk of malignancy.</p></abstract><textClass><keywords scheme="Journal Subject"><list><head>hwp-journal-coll</head><item><term>Immunology (including allergy)</term></item></list></keywords></textClass><textClass><keywords scheme="Journal Subject"><list><head>hwp-journal-coll</head><item><term>Biological agents</term></item></list></keywords></textClass><textClass><keywords scheme="Journal Subject"><list><head>hwp-journal-coll</head><item><term>Drugs: musculoskeletal and joint diseases</term></item></list></keywords></textClass><textClass><keywords scheme="Journal Subject"><list><head>hwp-journal-coll</head><item><term>Epidemiology</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2007-06-01">Created</change><change when="2008-01">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><extension>txt</extension><original>false</original><mimetype>text/plain</mimetype><uri>https://api.istex.fr/ark:/67375/NVC-KQHFPBGL-7/fulltext.txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="corpus bmj" wicri:toSee="no header"><istex:xmlDeclaration>version="1.0" encoding="UTF-8" standalone="no"</istex:xmlDeclaration><istex:docType PUBLIC="-//NLM//DTD Journal Archiving and Interchange DTD v2.3 20070202//EN" URI="archivearticle.dtd" name="istex:docType"></istex:docType><istex:document><article article-type="research-article" xml:lang="EN"><front><journal-meta><journal-id journal-id-type="hwp">annrheumdis</journal-id><journal-id journal-id-type="nlm-ta">Ann Rheum Dis</journal-id><journal-id journal-id-type="publisher-id">ard</journal-id><journal-title>Annals of the Rheumatic Diseases</journal-title><abbrev-journal-title abbrev-type="publisher">Ann Rheum Dis</abbrev-journal-title><issn pub-type="ppub">0003-4967</issn><issn pub-type="epub">1468-2060</issn><publisher><publisher-name>BMJ Publishing Group Ltd and European League Against Rheumatism</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">ar69039</article-id><article-id pub-id-type="doi">10.1136/ard.2006.069039</article-id><article-id pub-id-type="other">annrheumdis;67/1/74</article-id><article-id pub-id-type="other">annrheumdis;ard.2006.069039</article-id><article-id pub-id-type="pmid">17545189</article-id><article-id pub-id-type="other">74</article-id><article-id pub-id-type="other">ard.2006.069039</article-id><article-categories><subj-group subj-group-type="heading"><subject content-type="original">Extended reports</subject></subj-group><subj-group subj-group-type="hwp-journal-coll"><subject>Immunology (including allergy)</subject></subj-group><subj-group subj-group-type="hwp-journal-coll"><subject>Biological agents</subject></subj-group><subj-group subj-group-type="hwp-journal-coll"><subject>Drugs: musculoskeletal and joint diseases</subject></subj-group><subj-group subj-group-type="hwp-journal-coll"><subject>Epidemiology</subject></subj-group></article-categories><title-group><article-title>The relationship between cancer and medication exposures in systemic lupus erythaematosus: a case–cohort study</article-title><alt-title alt-title-type="running-head">Extended report</alt-title></title-group><contrib-group><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Bernatsky</surname><given-names>S</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Joseph</surname><given-names>L</given-names></name><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Boivin</surname><given-names>J-F</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Gordon</surname><given-names>C</given-names></name><xref ref-type="aff" rid="aff4">4</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Urowitz</surname><given-names>M</given-names></name><xref ref-type="aff" rid="aff5">5</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Gladman</surname><given-names>D</given-names></name><xref ref-type="aff" rid="aff5">5</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Fortin</surname><given-names>P R</given-names></name><xref ref-type="aff" rid="aff5">5</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Ginzler</surname><given-names>E</given-names></name><xref ref-type="aff" rid="aff6">6</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Bae</surname><given-names>S-C</given-names></name><xref ref-type="aff" rid="aff7">7</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Barr</surname><given-names>S</given-names></name><xref ref-type="aff" rid="aff8">8</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Edworthy</surname><given-names>S</given-names></name><xref ref-type="aff" rid="aff8">8</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Isenberg</surname><given-names>D</given-names></name><xref ref-type="aff" rid="aff9">9</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Rahman</surname><given-names>A</given-names></name><xref ref-type="aff" rid="aff9">9</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Petri</surname><given-names>M</given-names></name><xref ref-type="aff" rid="aff10">10</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Alarcón</surname><given-names>G S</given-names></name><xref ref-type="aff" rid="aff11">11</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Aranow</surname><given-names>C</given-names></name><xref ref-type="aff" rid="aff12">12</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Dooley</surname><given-names>M-A</given-names></name><xref ref-type="aff" rid="aff13">13</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Rajan</surname><given-names>R</given-names></name><xref ref-type="aff" rid="aff14">14</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Sénécal</surname><given-names>J-L</given-names></name><xref ref-type="aff" rid="aff15">15</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Zummer</surname><given-names>M</given-names></name><xref ref-type="aff" rid="aff16">16</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Manzi</surname><given-names>S</given-names></name><xref ref-type="aff" rid="aff17">17</xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Ramsey-Goldman</surname><given-names>R</given-names></name></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Clarke</surname><given-names>A E</given-names></name><xref ref-type="aff" rid="aff2">2</xref></contrib></contrib-group><aff id="aff1"><label>1</label><addr-line>Division of Clinical Epidemiology, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada</addr-line></aff><aff id="aff2"><label>2</label><addr-line>Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada</addr-line></aff><aff id="aff3"><label>3</label><addr-line>Department of Rheumatology, University of Birmingham, UK</addr-line></aff><aff id="aff4"><label>4</label><addr-line>Division of Health Care & Outcomes Research, Toronto Western Research Institute, Toronto, Ontario, Canada</addr-line></aff><aff id="aff5"><label>5</label><addr-line>Division of Rheumatology, Department of Medicine, SUNY Health Science Center at Brooklyn, New York, USA</addr-line></aff><aff id="aff6"><label>6</label><addr-line>Department of Internal Medicine, Division of Rheumatology, Hanyang University College of Medicine and the Hospital of Rheumatic Diseases, Seoul, Korea</addr-line></aff><aff id="aff7"><label>7</label><addr-line>Division of Rheumatology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada</addr-line></aff><aff id="aff8"><label>8</label><addr-line>Centre for Rheumatology Research - Department of Medicine, University College London, UK</addr-line></aff><aff id="aff9"><label>9</label><addr-line>Division of Rheumatology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA</addr-line></aff><aff id="aff10"><label>10</label><addr-line>Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama, Birmingham, Alabama, USA</addr-line></aff><aff id="aff11"><label>11</label><addr-line>Department of Medicine, Columbia University, New York, USA</addr-line></aff><aff id="aff12"><label>12</label><addr-line>Department of Medicine, Thurston Arthritis Research Center, The University of North Carolina at Chapel Hill, North Carolina, USA</addr-line></aff><aff id="aff13"><label>13</label><addr-line>Department of Oncology, McGill University Health Centre, Montreal, Quebec, Canada</addr-line></aff><aff id="aff14"><label>14</label><addr-line>Division of Rheumatology, Centre Hospitalier de l’Universite de Montreal, Department of Medicine, University of Montreal School of Medicine, Montreal, Quebec, Canada</addr-line></aff><aff id="aff15"><label>15</label><addr-line>Department of Rheumatology, Maisonneuve-Rosemont Hospital, Montreal, Quebec, Canada</addr-line></aff><aff id="aff16"><label>16</label><addr-line>Division of Rheumatology and Clinical Immunology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA</addr-line></aff><aff id="aff17"><label>17</label><addr-line>Division of Rheumatology, Northwestern University, Feinberg School of Medicine, Chicago, Illinois, USA</addr-line></aff><author-notes><corresp>Dr Sasha Bernatsky, Division of Clinical Epidemiology, McGill University Health Centre, 687 Pine Avenue West, V-Building, Montreal, Québec H3A 1A1, Canada; <email xlink:type="simple">sasha.bernatsky@mail.mcgill.ca</email></corresp></author-notes><pub-date pub-type="ppub"><month>1</month><year>2008</year></pub-date><pub-date pub-type="epub-original"><day>31</day><month>5</month><year>2007</year></pub-date><pub-date pub-type="epub"><day>1</day><month>6</month><year>2007</year></pub-date><volume>67</volume><volume-id pub-id-type="other">67</volume-id><volume-id pub-id-type="other">67</volume-id><issue>1</issue><issue-id pub-id-type="other">annrheumdis;67/1</issue-id><issue-id pub-id-type="other">1</issue-id><issue-id pub-id-type="other">67/1</issue-id><fpage>74</fpage><history><date date-type="accepted"><day>7</day><month>5</month><year>2007</year></date></history><permissions><copyright-statement>2008 BMJ Publishing Group and European League Against Rheumatism</copyright-statement><copyright-year>2008</copyright-year></permissions><self-uri content-type="pdf" xlink:role="full-text" xlink:href="annrheumdis-67-74.pdf"></self-uri><abstract><sec><title>Objective:</title><p>To examine if, in systemic lupus erythaematosus (SLE), exposure to immunosuppressive therapy (cyclophosphamide, azathioprine, methotrexate) increases cancer risk.</p></sec><sec><title>Methods:</title><p>A case–cohort study was performed within a multi-site international SLE cohort; subjects were linked to regional tumour registries to determine cancer cases occurring after entry into the cohort. We calculated the hazard ratio (HR) for cancer after exposure to an immunosuppressive drug, in models that controlled for other medications (anti-malarial drugs, systemic glucocorticoids, non-steroidal anti-inflammatory drugs (NSAIDs), aspirin), smoking, age, sex, race/ethnicity, geographic location, calendar year, SLE duration, and lupus damage scores. In the primary analyses, exposures were treated categorically (ever/never) and as time-dependent.</p></sec><sec><title>Results:</title><p>Results are presented from 246 cancer cases and 538 controls without cancer. The adjusted HR for overall cancer risk after any immunosuppressive drug was 0.82 (95% CI 0.50–1.36). Age ⩾65, and the presence of non-malignancy damage were associated with overall cancer risk. For lung cancer (n = 35 cases), smoking was also a prominent risk factor. When looking at haematological cancers specifically (n = 46 cases), there was a suggestion of an increased risk after immunosuppressive drug exposures, particularly when these were lagged by a period of 5 years (adjusted HR 2.29, 95% CI 1.02–5.15).</p></sec><sec><title>Conclusions:</title><p>In our SLE sample, age ⩾65, damage, and tobacco exposure were associated with cancer risk. Though immunosuppressive therapy may not be the principal driving factor for overall cancer risk, it may contribute to an increased risk of haematological malignancies. Future studies are in progress to evaluate independent influence of medication exposures and disease activity on risk of malignancy.</p></sec></abstract></article-meta></front></article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>The relationship between cancer and medication exposures in systemic lupus erythaematosus: a case–cohort study</title></titleInfo><titleInfo type="alternative" lang="en" contentType="CDATA"><title>The relationship between cancer and medication exposures in systemic lupus erythaematosus: a case–cohort study</title></titleInfo><name type="personal"><namePart type="given">S</namePart><namePart type="family">Bernatsky</namePart><affiliation>Division of Clinical Epidemiology, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">L</namePart><namePart type="family">Joseph</namePart><affiliation>Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">J-F</namePart><namePart type="family">Boivin</namePart><affiliation>Division of Clinical Epidemiology, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">C</namePart><namePart type="family">Gordon</namePart><affiliation>Division of Health Care & Outcomes Research, Toronto Western Research Institute, Toronto, Ontario, Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">M</namePart><namePart type="family">Urowitz</namePart><affiliation>Division of Rheumatology, Department of Medicine, SUNY Health Science Center at Brooklyn, New York, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">D</namePart><namePart type="family">Gladman</namePart><affiliation>Division of Rheumatology, Department of Medicine, SUNY Health Science Center at Brooklyn, New York, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">P R</namePart><namePart type="family">Fortin</namePart><affiliation>Division of Rheumatology, Department of Medicine, SUNY Health Science Center at Brooklyn, New York, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">E</namePart><namePart type="family">Ginzler</namePart><affiliation>Department of Internal Medicine, Division of Rheumatology, Hanyang University College of Medicine and the Hospital of Rheumatic Diseases, Seoul, Korea</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">S-C</namePart><namePart type="family">Bae</namePart><affiliation>Division of Rheumatology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">S</namePart><namePart type="family">Barr</namePart><affiliation>Centre for Rheumatology Research - Department of Medicine, University College London, UK</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">S</namePart><namePart type="family">Edworthy</namePart><affiliation>Centre for Rheumatology Research - Department of Medicine, University College London, UK</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">D</namePart><namePart type="family">Isenberg</namePart><affiliation>Division of Rheumatology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">A</namePart><namePart type="family">Rahman</namePart><affiliation>Division of Rheumatology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">M</namePart><namePart type="family">Petri</namePart><affiliation>Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama, Birmingham, Alabama, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">G S</namePart><namePart type="family">Alarcón</namePart><affiliation>Department of Medicine, Columbia University, New York, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">C</namePart><namePart type="family">Aranow</namePart><affiliation>Department of Medicine, Thurston Arthritis Research Center, The University of North Carolina at Chapel Hill, North Carolina, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">M-A</namePart><namePart type="family">Dooley</namePart><affiliation>Department of Oncology, McGill University Health Centre, Montreal, Quebec, Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">R</namePart><namePart type="family">Rajan</namePart><affiliation>Division of Rheumatology, Centre Hospitalier de l’Universite de Montreal, Department of Medicine, University of Montreal School of Medicine, Montreal, Quebec, Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">J-L</namePart><namePart type="family">Sénécal</namePart><affiliation>Department of Rheumatology, Maisonneuve-Rosemont Hospital, Montreal, Quebec, Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">M</namePart><namePart type="family">Zummer</namePart><affiliation>Division of Rheumatology and Clinical Immunology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">S</namePart><namePart type="family">Manzi</namePart><affiliation>Division of Rheumatology, Northwestern University, Feinberg School of Medicine, Chicago, Illinois, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">R</namePart><namePart type="family">Ramsey-Goldman</namePart><affiliation>1 Division of Clinical Epidemiology, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada</affiliation><affiliation>2 Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada</affiliation><affiliation>3 Department of Rheumatology, University of Birmingham, UK</affiliation><affiliation>4 Division of Health Care & Outcomes Research, Toronto Western Research Institute, Toronto, Ontario, Canada</affiliation><affiliation>5 Division of Rheumatology, Department of Medicine, SUNY Health Science Center at Brooklyn, New York, USA</affiliation><affiliation>6 Department of Internal Medicine, Division of Rheumatology, Hanyang University College of Medicine and the Hospital of Rheumatic Diseases, Seoul, Korea</affiliation><affiliation>7 Division of Rheumatology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada</affiliation><affiliation>8 Centre for Rheumatology Research - Department of Medicine, University College London, UK</affiliation><affiliation>9 Division of Rheumatology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA</affiliation><affiliation>10 Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama, Birmingham, Alabama, USA</affiliation><affiliation>11 Department of Medicine, Columbia University, New York, USA</affiliation><affiliation>12 Department of Medicine, Thurston Arthritis Research Center, The University of North Carolina at Chapel Hill, North Carolina, USA</affiliation><affiliation>13 Department of Oncology, McGill University Health Centre, Montreal, Quebec, Canada</affiliation><affiliation>14 Division of Rheumatology, Centre Hospitalier de l’Universite de Montreal, Department of Medicine, University of Montreal School of Medicine, Montreal, Quebec, Canada</affiliation><affiliation>15 Department of Rheumatology, Maisonneuve-Rosemont Hospital, Montreal, Quebec, Canada</affiliation><affiliation>16 Division of Rheumatology and Clinical Immunology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA</affiliation><affiliation>17 Division of Rheumatology, Northwestern University, Feinberg School of Medicine, Chicago, Illinois, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">A E</namePart><namePart type="family">Clarke</namePart><affiliation>Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="research-article" displayLabel="research-article" authority="ISTEX" authorityURI="https://content-type.data.istex.fr" valueURI="https://content-type.data.istex.fr/ark:/67375/XTP-1JC4F85T-7">research-article</genre><originInfo><publisher>BMJ Publishing Group Ltd and European League Against Rheumatism</publisher><dateIssued encoding="w3cdtf">2008-01</dateIssued><dateCreated encoding="w3cdtf">2007-06-01</dateCreated><copyrightDate encoding="w3cdtf">2008</copyrightDate></originInfo><language><languageTerm type="code" authority="iso639-2b">eng</languageTerm><languageTerm type="code" authority="rfc3066">en</languageTerm></language><abstract>Objective: To examine if, in systemic lupus erythaematosus (SLE), exposure to immunosuppressive therapy (cyclophosphamide, azathioprine, methotrexate) increases cancer risk. Methods: A case–cohort study was performed within a multi-site international SLE cohort; subjects were linked to regional tumour registries to determine cancer cases occurring after entry into the cohort. We calculated the hazard ratio (HR) for cancer after exposure to an immunosuppressive drug, in models that controlled for other medications (anti-malarial drugs, systemic glucocorticoids, non-steroidal anti-inflammatory drugs (NSAIDs), aspirin), smoking, age, sex, race/ethnicity, geographic location, calendar year, SLE duration, and lupus damage scores. In the primary analyses, exposures were treated categorically (ever/never) and as time-dependent. Results: Results are presented from 246 cancer cases and 538 controls without cancer. The adjusted HR for overall cancer risk after any immunosuppressive drug was 0.82 (95% CI 0.50–1.36). Age ⩾65, and the presence of non-malignancy damage were associated with overall cancer risk. For lung cancer (n = 35 cases), smoking was also a prominent risk factor. When looking at haematological cancers specifically (n = 46 cases), there was a suggestion of an increased risk after immunosuppressive drug exposures, particularly when these were lagged by a period of 5 years (adjusted HR 2.29, 95% CI 1.02–5.15). Conclusions: In our SLE sample, age ⩾65, damage, and tobacco exposure were associated with cancer risk. Though immunosuppressive therapy may not be the principal driving factor for overall cancer risk, it may contribute to an increased risk of haematological malignancies. Future studies are in progress to evaluate independent influence of medication exposures and disease activity on risk of malignancy.</abstract><relatedItem type="host"><titleInfo><title>Annals of the Rheumatic Diseases</title></titleInfo><titleInfo type="abbreviated"><title>Ann Rheum Dis</title></titleInfo><genre type="journal" authority="ISTEX" authorityURI="https://publication-type.data.istex.fr" valueURI="https://publication-type.data.istex.fr/ark:/67375/JMC-0GLKJH51-B">journal</genre><subject><genre>hwp-journal-coll</genre><topic>Immunology (including allergy)</topic></subject><subject><genre>hwp-journal-coll</genre><topic>Biological agents</topic></subject><subject><genre>hwp-journal-coll</genre><topic>Drugs: musculoskeletal and joint diseases</topic></subject><subject><genre>hwp-journal-coll</genre><topic>Epidemiology</topic></subject><identifier type="ISSN">0003-4967</identifier><identifier type="eISSN">1468-2060</identifier><identifier type="PublisherID">ard</identifier><identifier type="PublisherID-hwp">annrheumdis</identifier><identifier type="PublisherID-nlm-ta">Ann Rheum Dis</identifier><part><date>2008</date><detail type="volume"><caption>vol.</caption><number>67</number></detail><detail type="issue"><caption>no.</caption><number>1</number></detail><extent unit="pages"><start>74</start></extent></part></relatedItem><identifier type="istex">A4ED4E047016C31087BDE29E164614EA04E5C400</identifier><identifier type="ark">ark:/67375/NVC-KQHFPBGL-7</identifier><identifier type="DOI">10.1136/ard.2006.069039</identifier><identifier type="href">annrheumdis-67-74.pdf</identifier><identifier type="ArticleID">ar69039</identifier><identifier type="PMID">17545189</identifier><identifier type="local">annrheumdis;67/1/74</identifier><accessCondition type="use and reproduction" contentType="copyright">2008 BMJ Publishing Group and European League Against Rheumatism</accessCondition><recordInfo><recordContentSource authority="ISTEX" authorityURI="https://loaded-corpus.data.istex.fr" valueURI="https://loaded-corpus.data.istex.fr/ark:/67375/XBH-7M42M2QJ-2">bmj</recordContentSource><recordOrigin>2008 BMJ Publishing Group and European League Against Rheumatism</recordOrigin></recordInfo></mods><json:item><extension>json</extension><original>false</original><mimetype>application/json</mimetype><uri>https://api.istex.fr/ark:/67375/NVC-KQHFPBGL-7/record.json</uri></json:item></metadata><annexes><json:item><extension>jpeg</extension><original>true</original><mimetype>image/jpeg</mimetype><uri>https://api.istex.fr/ark:/67375/NVC-KQHFPBGL-7/annexes.jpeg</uri></json:item></annexes><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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