title: Seasonal variation in the patient diagnosis of primary biliary cirrhosis: further evidence for an environmental component to etiology.
abstract: The etiology of primary biliary cirrhosis (PBC) is far from clear. Both genetic and environmental factors are likely to be involved. We have previously reported evidence of space-time clustering, suggesting that a transient environmental agent may be involved in etiology. To further examine whether a seasonally varying environmental agent may contribute to the etiology of PBC, we have analyzed seasonal variation with respect to month of diagnosis using population-based data from northeast England over a defined period (1987-2003). Date of diagnosis was defined as the earliest date at which the patient was found to have fulfilled any two of three diagnostic criteria (i.e., antimitochondrial antibody-positive titer ≥1 in 40, cholestatic liver blood tests, diagnostic or compatible liver histology). Monthly expected (E) numbers of cases were calculated under an assumption of a uniform distribution throughout the year. Observed counts (O) were compared with the expected numbers. The chi-squared heterogeneity test was used to test for overall nonuniform variation and also for individual months. Poisson regression analysis was used to fit a sinusoidal (i.e., harmonic) model to the data, using month of diagnosis as a covariate in the model. There was a marked peak for diagnoses in the month of June (O = 115, E = 84.7, O/E = 1.36; P = 0.001). Furthermore, there was evidence of a sinusoidal pattern with a June peak (P = 0.012).
  
  
  CONCLUSIONS
  These highly novel results provide further evidence for the involvement of a seasonally varying environmental agent in the etiology of PBC.
authors.affiliation: Institute of Health and Society, Newcastle University, Newcastle upon Tyne, United Kingdom. Richard.McNally@ncl.ac.uk
authors.forename: Richard J Q
authors.initials: RJ
authors.lastname: McNally
authors.forename: Peter W
authors.initials: PW
authors.lastname: James
authors.forename: Samantha
authors.initials: S
authors.lastname: Ducker
authors.forename: Oliver F W
authors.initials: OF
authors.lastname: James
mesh_terms: D004739:England / Q000453:epidemiology; D004777:Environment; D006801:Humans; D008099:Liver / Q000473:pathology; D008105:Liver Cirrhosis, Biliary / Q000175:diagnosis* / Q000453:epidemiology / Q000209:etiology / Q000401:mortality; D012621:Seasons