title: The relationship between serum ghrelin and the risk of gastric and esophagogastric junctional adenocarcinomas.
abstract: BACKGROUND
  Cancers of the upper gastrointestinal tract remain a substantial cause of morbidity and mortality worldwide. Ghrelin is a hormone produced in the oxyntic glands of the stomach, and under conditions of chronic inflammation and atrophy, serum ghrelin concentrations decrease. However, the relationship between ghrelin and the risk of gastric and esophagogastric junctional cancers has not been investigated.
  
  
  METHODS
  We conducted a nested case-control study within the Finnish Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study to examine the relationship between serum ghrelin concentration and the risk of gastric noncardia adenocarcinoma (GNCA) and esophagogastric junctional adenocarcinoma (EGJA). Data from 261 GNCA patients, 98 EGJA patients, and 441 control subjects were analyzed. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using logistic regression with adjustment for potential confounders. Lag analysis was also performed to investigate the temporal nature of the associations between baseline serum pepsinogen I and ghrelin in GNCA and EGJA patients. All statistical tests were two-sided.
  
  
  RESULTS
  Lower concentrations of serum ghrelin were statistically significantly associated with an increased risk of both GNCA (adjusted OR = 1.75, 95% CI = 1.49 to 2.04; P < .001) and EGJA (adjusted OR = 1.56, 95% CI = 1.28 to 1.89, P < .001). A multivariable model found that the risk of both GNCA and EGJA were statistically significantly increased for those individuals in the lowest quartile of serum ghrelin levels compared with those in the highest quartile (OR of GNCA = 5.63, 95% CI = 3.16 to 10.03; OR of EGJA = 4.90, 95% CI = 2.11 to 11.35). The statistical significance of these associations remained even after restricting the analysis to those patients who developed cancer more than 10 years after baseline serum ghrelin measurements.
  
  
  CONCLUSIONS
  Low baseline concentrations of serum ghrelin were associated with a statistically significant increase in the risk of GNCA and EGJA, suggesting a potential role for gastric hormones in carcinogenesis.
authors.affiliation: Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Blvd, EPS 3034, Rockville, MD 20892, USA. murphygw@mail.nih.gov
authors.forename: Gwen
authors.initials: G
authors.lastname: Murphy
authors.forename: Farin
authors.initials: F
authors.lastname: Kamangar
authors.forename: Sanford M
authors.initials: SM
authors.lastname: Dawsey
authors.forename: Frank Z
authors.initials: FZ
authors.lastname: Stanczyk
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Weinstein
authors.forename: Philip R
authors.initials: PR
authors.lastname: Taylor
authors.forename: Jarmo
authors.initials: J
authors.lastname: Virtamo
authors.forename: Christian C
authors.initials: CC
authors.lastname: Abnet
authors.forename: Demetrius
authors.initials: D
authors.lastname: Albanes
authors.forename: Neal D
authors.initials: ND
authors.lastname: Freedman
mesh_terms: D000230:Adenocarcinoma / Q000097:blood* / Q000453:epidemiology* / Q000382:microbiology; D000368:Aged; D000907:Antibodies, Bacterial / Q000097:blood; D014408:Biomarkers, Tumor / Q000097:blood*; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D004943:Esophagogastric Junction; D005260:Female; D005387:Finland / Q000453:epidemiology; D054439:Ghrelin / Q000097:blood*; D016481:Helicobacter Infections / Q000150:complications; D016480:Helicobacter pylori / Q000302:isolation & purification; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D020116:Pepsinogen A / Q000097:blood*; D011446:Prospective Studies; D011863:Radioimmunoassay; D018570:Risk Assessment; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000097:blood* / Q000453:epidemiology* / Q000382:microbiology
chemical_list: D000907:Antibodies, Bacterial; D014408:Biomarkers, Tumor; D054439:Ghrelin; D020116:Pepsinogen A