title: Persistent chronic inflammation contributes to the development of cancer in patients with rheumatoid arthritis from a defined population of northwestern Spain.
abstract: OBJECTIVE
  We assessed the contribution of clinical features, routine laboratory markers of inflammation, HLA-DRB1 alleles, and methotrexate therapy to cancer incidence and mortality in a cohort of rheumatoid arthritis (RA) patients prospectively followed at the single referral center for an area of Northwestern Spain.
  
  
  METHODS
  Patients fulfilling the 1987 American College of Rheumatology classification criteria for RA seen at the rheumatology outpatient clinic of Hospital Xeral Calde, Lugo between March and September 1996 were included. HLA-DRB1 phenotype, epidemiological and clinical data from the time of RA diagnosis were assessed at that time. Afterward, patients were prospectively followed and clinical records were examined until the patient's death or September 1, 2005. Presence of histologically confirmed diagnosis of cancer was assessed over the extended follow-up in all cases.
  
  
  RESULTS
  One hundred eighty-two consecutive patients were assessed. Compared with the general Spanish population, the age- and gender-standardized mortality ratio for cancer was 1.01 (95% confidence interval: 0.49 to 1.75). Cancer mortality adjusted by age and sex was associated with chronic inflammation determined by C-reactive protein (CRP) (hazard ratio, HR, = 1.15; P < 0.001), and erythrocyte sedimentation rate (ESR) (HR = 1.05; P = 0.006). Increased risk of cancer was also associated with CRP (HR = 1.13; P = 0.001), ESR (HR = 1.04; P = 0.02), and the HLA-DRB1*0404 allele (HR = 3.24; P = 0.05).
  
  
  CONCLUSIONS
  This study does not support an increased mortality due to cancer in RA patients from Northwestern Spain. However, the present data indicate that high-grade inflammation contributes to both the risk and the mortality of cancer in RA.
authors.affiliation: Group of Epidemiology and Computational Biology, School of Medicine, University of Cantabria, Santander, Spain. llorcaj@unican.es
authors.forename: Javier
authors.initials: J
authors.lastname: Llorca
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Lopez-Diaz
authors.forename: Carlos
authors.initials: C
authors.lastname: Gonzalez-Juanatey
authors.forename: William E R
authors.initials: WE
authors.lastname: Ollier
authors.forename: Javier
authors.initials: J
authors.lastname: Martin
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Gonzalez-Gay
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000401:mortality*; D002908:Chronic Disease; D015897:Comorbidity; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D007249:Inflammation / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000401:mortality*; D011446:Prospective Studies; D012307:Risk Factors; D013030:Spain / Q000453:epidemiology