title: Smoking is a major preventable risk factor for rheumatoid arthritis: estimations of risks after various exposures to cigarette smoke.
abstract: BACKGROUND
  Earlier studies have demonstrated that smoking and genetic risk factors interact in providing an increased risk of rheumatoid arthritis (RA). Less is known on how smoking contributes to RA in the context of genetic variability, and what proportion of RA may be caused by smoking.
  
  
  OBJECTIVE
  To determine the association between the amount of smoking and risk of RA in the context of different HLA-DRB1 shared epitope (SE) alleles, and to estimate proportions of RA cases attributed to smoking.
  
  
  METHODS
  Setting and Participants Data from the Swedish Epidemiological Investigation of Rheumatoid Arthritis (EIRA) case-control study encompassing 1204 cases and 871 controls were analysed. Main Outcome Measure Estimated OR to develop RA and excess fraction of cases attributable to smoking according to the amount of smoking and genotype.
  
  
  RESULTS
  Smoking was estimated to be responsible for 35% of anticitrullinated protein/peptide antibody (ACPA)-positive cases. For each HLA-DRB1 SE genotype, smoking was dose-dependently associated with an increased risk of ACPA-positive RA (p trend <0.001). In individuals carrying two copies of the HLA-DRB1 SE, 55% of ACPA-positive RA was attributable to smoking.
  
  
  CONCLUSIONS
  Smoking is a preventable risk factor for RA. The increased risk due to smoking is dependent on the amount of smoking and genotype.
authors.affiliation: Correspondence to Dr Henrik Källberg, Institute of Environmental Medicine, Box 210, Karolinska Institutet, 171 77 Stockholm, Sweden. henrik.kallberg@ki.se
authors.forename: Henrik
authors.initials: H
authors.lastname: Källberg
authors.forename: Bo
authors.initials: B
authors.lastname: Ding
authors.forename: Leonid
authors.initials: L
authors.lastname: Padyukov
authors.forename: Camilla
authors.initials: C
authors.lastname: Bengtsson
authors.forename: Johan
authors.initials: J
authors.lastname: Rönnelid
authors.forename: Lars
authors.initials: L
authors.lastname: Klareskog
authors.forename: Lars
authors.initials: L
authors.lastname: Alfredsson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D001323:Autoantibodies / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D006801:Humans; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology; D011634:Public Health; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects* / Q000453:epidemiology; D013548:Sweden / Q000453:epidemiology; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide