title: Age-specific risk factor profiles of adenocarcinomas of the esophagus: A pooled analysis from the international BEACON consortium.
abstract: Esophageal (EA) and esophagogastric junction (EGJA) adenocarcinoma have been steadily increasing in frequency in younger people; however, the etiology of these cancers is poorly understood. We therefore investigated associations of body mass index (BMI), cigarette smoking, alcohol consumption, gastroesophageal reflux and use of nonsteroidal anti-inflammatory drugs (NSAIDs) in relation to age-specific risks of EA and EGJA. We pooled individual participant data from eight population-based, case-control studies within the international Barrett's and Esophageal Adenocarcinoma Consortium (BEACON). The analysis included 1,363 EA patients, 1,472 EGJA patients and 5,728 control participants. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for age-specific (<50, 50-59, 60-69, ≥70 years) cancer outcomes, as well as interactions by age. BMI, smoking status and pack-years, recurrent gastroesophageal reflux and frequency of gastroesophageal reflux were positively associated with EA and EGJA in each age group. Early-onset EA (<50 years) had stronger associations with recurrent gastroesophageal reflux (OR = 8.06, 95% CI: 4.52, 14.37; peffect modification  = 0.01) and BMI (ORBMI ≥ 30 vs . <25  = 4.19, 95% CI: 2.23, 7.87; peffect modification  = 0.04), relative to older age groups. In contrast, inverse associations of NSAID use were strongest in the oldest age group (≥70 years), although this apparent difference was not statistically significant. Age-specific associations with EGJA showed similar, but slightly weaker patterns and no statistically significant differences by age were observed. Our study provides evidence that associations between obesity and gastroesophageal reflux are stronger among earlier onset EA cancers.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Drahos
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD.
authors.forename: Qian
authors.initials: Q
authors.lastname: Xiao
authors.affiliation: Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT.
authors.forename: Harvey A
authors.initials: HA
authors.lastname: Risch
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD.
authors.forename: Neal D
authors.initials: ND
authors.lastname: Freedman
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD.
authors.forename: Christian C
authors.initials: CC
authors.lastname: Abnet
authors.affiliation: Centre for Public Health, Queen's University, Belfast, Northern Ireland.
authors.forename: Lesley A
authors.initials: LA
authors.lastname: Anderson
authors.affiliation: Department of Population Sciences, Beckman Research Institute and City of Hope Comprehensive Cancer Center, Duarte, CA.
authors.forename: Leslie
authors.initials: L
authors.lastname: Bernstein
authors.affiliation: RTI International, Rockville, MD.
authors.forename: Linda
authors.initials: L
authors.lastname: Brown
authors.affiliation: Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Wong-Ho
authors.initials: WH
authors.lastname: Chow
authors.affiliation: Department of Epidemiology, University of North Carolina School, Chapel Hill, NC.
authors.forename: Marilie D
authors.initials: MD
authors.lastname: Gammon
authors.affiliation: Department of Public Health Analysis, School of Community Health and Policy, Morgan State University, Baltimore, MD.
authors.forename: Farin
authors.initials: F
authors.lastname: Kamangar
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD.
authors.forename: Linda M
authors.initials: LM
authors.lastname: Liao
authors.affiliation: Centre for Public Health, Queen's University, Belfast, Northern Ireland.
authors.forename: Liam J
authors.initials: LJ
authors.lastname: Murray
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD.
authors.forename: Mary H
authors.initials: MH
authors.lastname: Ward
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Weimin
authors.initials: W
authors.lastname: Ye
authors.affiliation: Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA.
authors.forename: Anna H
authors.initials: AH
authors.lastname: Wu
authors.affiliation: Program in Epidemiology, Fred Hutchinson Cancer Research Center, Seattle, WA.
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Vaughan
authors.affiliation: Population Health, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
authors.forename: David C
authors.initials: DC
authors.lastname: Whiteman
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Cook
mesh_terms: D000230:Adenocarcinoma / Q000453:epidemiology* / Q000209:etiology*; D000328:Adult; D000367:Age Factors; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000428:Alcohol Drinking; D001471:Barrett Esophagus / Q000150:complications; D004938:Esophageal Neoplasms / Q000453:epidemiology* / Q000209:etiology*; D005260:Female; D005764:Gastroesophageal Reflux / Q000150:complications; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D012307:Risk Factors; D012907:Smoking
keywords: age of onset; case-control studies; esophageal cancer; obesity; risk factors