title: Cigarette smoking, appendectomy, and tonsillectomy as risk factors for the development of primary sclerosing cholangitis: a case control study.
abstract: OBJECTIVE
  The strong clinical association between primary sclerosing cholangitis (PSC) and ulcerative colitis (UC) suggests common factors in their pathogenesis. Smoking, previous appendectomy, and tonsillectomy have been associated with a decreased risk of developing UC. In this study, our aim was to examine these risk factors in patients with PSC with and without underlying inflammatory bowel disease (IBD).
  
  
  METHODS
  The smoking habits and history of previous appendectomy and/or tonsillectomy of 170 patients with PSC, 41 without underlying IBD, 170 patients with UC but normal liver function tests, and 170 age and sex matched community controls were obtained by questionnaire.
  
  
  RESULTS
  A total of 112 PSC patients (66%) had never smoked compared with 66 controls (39%). Only 12 PSC patients (7%) were current smokers versus 43 controls (25%). The resultant odds ratio of having PSC was 0.17 (95% confidence interval (CI) 0.08-0.35) among current smokers and 0.33 (95% CI 0.21-0.52) among ever (former+current) smokers. Among former smokers, the odds of having PSC were also significantly decreased (odds ratio 0.45, 95% CI 0.26-0.73; p<0.05). In the subgroup of PSC patients without IBD, only 5% were current smokers versus 26% of matched controls, and never smokers were overrepresented (68% v 37%). The rate of previous appendectomy was similar in all three study groups (14%, 12%, and 13%) but the frequency of tonsillectomy was reduced in the PSC group (21% v 31%; p=0.05).
  
  
  CONCLUSIONS
  PSC, like UC, is a disease of non-smokers as the odds of having PSC was significantly decreased among current and former smokers. The association between non-smoking and PSC was independent of whether the PSC patient had underlying IBD. Previous tonsillectomy but not appendectomy may also be associated with a decreased risk of PSC but this warrants further study.
authors.affiliation: Department of Gastroenterology, Oxford Radcliffe Hospital, Oxford, UK.
authors.forename: S A
authors.initials: SA
authors.lastname: Mitchell
authors.forename: M
authors.initials: M
authors.lastname: Thyssen
authors.forename: T R
authors.initials: TR
authors.lastname: Orchard
authors.forename: D P
authors.initials: DP
authors.lastname: Jewell
authors.forename: K A
authors.initials: KA
authors.lastname: Fleming
authors.forename: R W
authors.initials: RW
authors.lastname: Chapman
mesh_terms: D000328:Adult; D000368:Aged; D001062:Appendectomy / Q000009:adverse effects*; D016022:Case-Control Studies; D015209:Cholangitis, Sclerosing / Q000209:etiology*; D003093:Colitis, Ulcerative / Q000209:etiology; D003424:Crohn Disease / Q000209:etiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*; D014068:Tonsillectomy / Q000009:adverse effects*