title: Is opium a real risk factor for esophageal cancer or just a methodological artifact? Hospital and neighborhood controls in case-control studies.
abstract: BACKGROUND
  Control selection is a major challenge in epidemiologic case-control studies. The aim of our study was to evaluate using hospital versus neighborhood control groups in studying risk factors of esophageal squamous cell carcinoma (ESCC).
  
  
  RESULTS
  We compared the results of two different case-control studies of ESCC conducted in the same region by a single research group. Case definition and enrollment were the same in the two studies, but control selection differed. In the first study, we selected two age- and sex-matched controls from inpatient subjects in hospitals, while for the second we selected two age- and sex-matched controls from each subject's neighborhood of residence. We used the test of heterogeneity to compare the results of the two studies. We found no significant differences in exposure data for tobacco-related variables such as cigarette smoking, chewing Nass (a tobacco product) and hookah (water pipe) usage, but the frequency of opium usage was significantly different between hospital and neighborhood controls. Consequently, the inference drawn for the association between ESCC and tobacco use did not differ between the studies, but it did for opium use. In the study using neighborhood controls, opium use was associated with a significantly increased risk of ESCC (adjusted OR 1.77, 95% CI 1.17-2.68), while in the study using hospital controls, this was not the case (OR 1.09, 95% CI 0.63-1.87). Comparing the prevalence of opium consumption in the two control groups and a cohort enrolled from the same geographic area suggested that the neighborhood controls were more representative of the study base population for this exposure.
  
  
  CONCLUSIONS
  Hospital and neighborhood controls did not lead us to the same conclusion for a major hypothesized risk factor for ESCC in this population. Our results show that control group selection is critical in drawing appropriate conclusions in observational studies.
authors.affiliation: Digestive Disease Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Ramin
authors.initials: R
authors.lastname: Shakeri
authors.forename: Farin
authors.initials: F
authors.lastname: Kamangar
authors.forename: Dariush
authors.initials: D
authors.lastname: Nasrollahzadeh
authors.forename: Mehdi
authors.initials: M
authors.lastname: Nouraie
authors.forename: Hooman
authors.initials: H
authors.lastname: Khademi
authors.forename: Arash
authors.initials: A
authors.lastname: Etemadi
authors.forename: Farhad
authors.initials: F
authors.lastname: Islami
authors.forename: Hajiamin
authors.initials: H
authors.lastname: Marjani
authors.forename: Saman
authors.initials: S
authors.lastname: Fahimi
authors.forename: Alireza
authors.initials: A
authors.lastname: Sepehr
authors.forename: Atieh
authors.initials: A
authors.lastname: Rahmati
authors.forename: Christian C
authors.initials: CC
authors.lastname: Abnet
authors.forename: Sanford M
authors.initials: SM
authors.lastname: Dawsey
authors.forename: Paul
authors.initials: P
authors.lastname: Brennan
authors.forename: Paolo
authors.initials: P
authors.lastname: Boffetta
authors.forename: Reza
authors.initials: R
authors.lastname: Malekzadeh
authors.forename: Reza
authors.initials: R
authors.lastname: Majdzadeh
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000209:etiology*; D016022:Case-Control Studies; D004938:Esophageal Neoplasms / Q000209:etiology*; D005260:Female; D006761:Hospitals; D006801:Humans; D007297:Inpatients; D007492:Iran; D008297:Male; D008875:Middle Aged; D009892:Opium / Q000009:adverse effects*; D015995:Prevalence; D012107:Research Design; D012111:Residence Characteristics; D012307:Risk Factors; D012737:Sex Factors; D012907:Smoking / Q000009:adverse effects
chemical_list: D009892:Opium