title: Acid-suppressing therapies and subsite-specific risk of stomach cancer.
abstract: BACKGROUND
  Associations of stomach cancer risk with histamine type-2 receptor antagonists (H2RA) and proton-pump inhibitors (PPI) are controversial. We hypothesised that proximal extension of Helicobacter pylori infection from acid suppression would disproportionately increase cancers at proximal subsites.
  
  
  METHODS
  A total of 1 563 860 individuals in the Danish Prescription Drug Registry first prescribed acid-suppressive drugs 1995-2011 were matched to unexposed population-based controls. Hazard ratios (HR) were calculated by Cox proportional hazard regression for stomach cancers diagnosed more than one year after first prescription.
  
  
  RESULTS
  There were 703 stomach cancers among H2RA-exposed individuals and 1347 among PPI-exposed. Restricted to individuals with five or more prescriptions, subsite-specific HRs for H2RA and PPI were 4.1 and 6.4 for proximal subsites vs 8.0 and 10.3 for distal subsites, respectively.
  
  
  CONCLUSIONS
  Moderate exposures to acid-suppressive drugs did not favour proximal tumour localisation. Given confounding by indication, these findings do not resolve potential contribution to gastric carcinogenesis overall.
authors.affiliation: Department of Epidemiology Research, Statens Serum Institut, DK-2300 Copenhagen S, Denmark.
authors.forename: E Christina M
authors.initials: ECM
authors.lastname: Wennerström
authors.affiliation: Department of Epidemiology Research, Statens Serum Institut, DK-2300 Copenhagen S, Denmark.
authors.forename: Jacob
authors.initials: J
authors.lastname: Simonsen
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD 20892, USA.
authors.forename: M Constanza
authors.initials: MC
authors.lastname: Camargo
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD 20892, USA.
authors.forename: Charles S
authors.initials: CS
authors.lastname: Rabkin
mesh_terms: D000143:Acids / Q000378:metabolism; D003718:Denmark; D005753:Gastric Mucosa / Q000378:metabolism; D016481:Helicobacter Infections / Q000150:complications / Q000188:drug therapy* / Q000453:epidemiology; D016480:Helicobacter pylori / Q000187:drug effects / Q000472:pathogenicity; D006635:Histamine H2 Antagonists / Q000009:adverse effects*; D006801:Humans; D016016:Proportional Hazards Models; D054328:Proton Pump Inhibitors / Q000009:adverse effects*; D012307:Risk Factors; D013270:Stomach / Q000187:drug effects / Q000473:pathology; D013274:Stomach Neoplasms / Q000139:chemically induced / Q000453:epidemiology* / Q000382:microbiology
chemical_list: D000143:Acids; D006635:Histamine H2 Antagonists; D054328:Proton Pump Inhibitors