title: The importance of exposure rate on odds ratios by cigarette smoking and alcohol consumption for esophageal adenocarcinoma and squamous cell carcinoma in the Barrett's Esophagus and Esophageal Adenocarcinoma Consortium.
abstract: BACKGROUND
  Cigarette smoking is associated with esophageal adenocarcinoma (EAC), esophagogastric junctional adenocarcinoma (EGJA) and esophageal squamous cell carcinoma (ESCC), and alcohol consumption with ESCC. However, no analyses have examined how delivery rate modifies the strength of odds ratio (OR) trends with total exposure, i.e., the impact on the OR for a fixed total exposure of high exposure rate for short duration compared with low exposure rate for long duration.
  
  
  METHODS
  The authors pooled data from 12 case-control studies from the Barrett's Esophagus and Esophageal Adenocarcinoma Consortium (BEACON), including 1242 (EAC), 1263 (EGJA) and 954 (ESCC) cases and 7053 controls, modeled joint ORs for cumulative exposure and exposure rate for cigarette smoking and alcohol consumption, and evaluated effect modification by sex, body mass index (BMI), age and self-reported acid reflux.
  
  
  RESULTS
  For smoking, all sites exhibited inverse delivery rate effects, whereby ORs with pack-years increased, but trends weakened with increasing cigarettes/day. None of the examined factors modified associations, except for ESCC where younger ages at diagnosis enhanced smoking effects (P<0.01). For EAC and EGJA, ORs with drink-years exhibited inverse associations in <5 drinks/day consumers and no association in heavier consumers. For ESCC, ORs with drink-years increased, with trends strengthening with greater drinks/day. There was no significant effect modification, except for EAC and EGJA where acid reflux mitigated the inverse associations (P=0.02). For ESCC, younger ages at diagnosis enhanced drinking-related ORs (P<0.01).
  
  
  CONCLUSIONS
  Patterns of ORs by pack-years and drink-years, delivery rate effects and effect modifiers revealed common as well as distinct etiologic elements for these diseases.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH/DHHS, Bethesda, MD 20892, USA. lubinj@mail.nih.gov
authors.forename: Jay H
authors.initials: JH
authors.lastname: Lubin
authors.forename: Michael B
authors.initials: MB
authors.lastname: Cook
authors.forename: Nirmala
authors.initials: N
authors.lastname: Pandeya
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Vaughan
authors.forename: Christian C
authors.initials: CC
authors.lastname: Abnet
authors.forename: Carol
authors.initials: C
authors.lastname: Giffen
authors.forename: Penelope M
authors.initials: PM
authors.lastname: Webb
authors.forename: Liam J
authors.initials: LJ
authors.lastname: Murray
authors.forename: Alan G
authors.initials: AG
authors.lastname: Casson
authors.forename: Harvey A
authors.initials: HA
authors.lastname: Risch
authors.forename: Weimin
authors.initials: W
authors.lastname: Ye
authors.forename: Farin
authors.initials: F
authors.lastname: Kamangar
authors.forename: Leslie
authors.initials: L
authors.lastname: Bernstein
authors.forename: Linda
authors.initials: L
authors.lastname: Sharp
authors.forename: Olof
authors.initials: O
authors.lastname: Nyrén
authors.forename: Marilie D
authors.initials: MD
authors.lastname: Gammon
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Corley
authors.forename: Anna H
authors.initials: AH
authors.lastname: Wu
authors.forename: Linda M
authors.initials: LM
authors.lastname: Brown
authors.forename: Wong-Ho
authors.initials: WH
authors.lastname: Chow
authors.forename: Mary H
authors.initials: MH
authors.lastname: Ward
authors.forename: Neal D
authors.initials: ND
authors.lastname: Freedman
authors.forename: David C
authors.initials: DC
authors.lastname: Whiteman
mesh_terms: D000230:Adenocarcinoma / Q000453:epidemiology* / Q000209:etiology; D000367:Age Factors; D000368:Aged; D000428:Alcohol Drinking / Q000009:adverse effects* / Q000453:epidemiology; D015992:Body Mass Index; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology* / Q000209:etiology; D016022:Case-Control Studies; D004938:Esophageal Neoplasms / Q000453:epidemiology* / Q000209:etiology; D004943:Esophagogastric Junction / Q000473:pathology; D005260:Female; D005764:Gastroesophageal Reflux / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D016017:Odds Ratio; D012307:Risk Factors; D012737:Sex Factors; D012907:Smoking / Q000009:adverse effects* / Q000453:epidemiology; D013997:Time Factors