title: Assessment of familiality, obesity, and other risk factors for early age of cancer diagnosis in adenocarcinomas of the esophagus and gastroesophageal junction.
abstract: OBJECTIVE
  Adenocarcinomas of the esophagus and adenocarcinomas of the gastroesophageal junction are postulated to be complex genetic diseases. Combined influences of environmental factors and genetic susceptibility likely influence the age at which these cancers develop. The aim of this study was to determine whether familiality and other recognized risk factors are associated with the development of these cancers at an earlier age.
  
  
  METHODS
  A structured validated questionnaire was utilized to collect self-reported data on gastro-esophageal reflux symptoms, risk factors for Barrett's esophagus (BE) and family history, including age of cancer diagnosis in affected relatives from probands with BE, adenocarcinoma of the esophagus, or adenocarcinoma of the gastroesophageal junction, at five tertiary care academic hospitals. Medical records of all relatives reported to be affected were requested from hospitals providing this cancer care to confirm family histories. Familiality of BE/cancer, obesity (defined as body mass index >30), gastroesophageal reflux symptoms, and other risk factors were assessed for association with a young age of cancer diagnosis.
  
  
  RESULTS
  A total of 356, 216 non-familial and 140 familial, cancers were studied. The study population consisted of 292 (82%) men and 64 (18%) women. Mean age of cancer diagnosis was no different in a comparison of familial and non-familial cancers, 62.6 vs. 61.9 years, P=0.70. There were also no significant differences in symptoms of gastroesophageal reflux, body mass index, race, gender, and smoking history between familial and non-familial cancers. Mean age of cancer diagnosis was significantly younger in those who were obese 1 year before diagnosis as compared to those who were non-obese, mean age 58.99 vs. 63.6 years, P=0.008. Multivariable modeling of age at cancer diagnosis showed that obesity 1 year before diagnosis was associated with a younger age of cancer diagnosis (P=0.005) after adjustment for heartburn and regurgitation duration.
  
  
  CONCLUSIONS
  Obesity is associated with the development of esophageal and gastroesophageal junctional adenocarcinomas at an earlier age. Familial cancers arise at the same age as non-familial cancers and have a similar risk factor profile.
authors.affiliation: Division of Gastroenterology, University Hospitals - Case Medical Center, Case Western Reserve University School of Medicine, 11100 Euclid Avenue, Cleveland, Ohio 44106, USA. Amitabh.chak@case.edu
authors.forename: Amitabh
authors.initials: A
authors.lastname: Chak
authors.forename: Gary
authors.initials: G
authors.lastname: Falk
authors.forename: William M
authors.initials: WM
authors.lastname: Grady
authors.forename: Margaret
authors.initials: M
authors.lastname: Kinnard
authors.forename: Robert
authors.initials: R
authors.lastname: Elston
authors.forename: Sumeet
authors.initials: S
authors.lastname: Mittal
authors.forename: James F
authors.initials: JF
authors.lastname: King
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Willis
authors.forename: Anokh
authors.initials: A
authors.lastname: Kondru
authors.forename: Wendy
authors.initials: W
authors.lastname: Brock
authors.forename: Jill
authors.initials: J
authors.lastname: Barnholtz-Sloan
mesh_terms: D000230:Adenocarcinoma / Q000453:epidemiology* / Q000209:etiology / Q000235:genetics*; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D004938:Esophageal Neoplasms / Q000453:epidemiology* / Q000209:etiology / Q000235:genetics*; D004943:Esophagogastric Junction; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications*; D018570:Risk Assessment; D012307:Risk Factors; D055815:Young Adult