title: IGF2R polymorphisms and risk of esophageal and gastric adenocarcinomas.
abstract: The mannose-6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R) encodes a protein that plays a critical role in tumor suppression, in part by modulating bioavailability of a potent mitogen, insulin-like growth factor-2 (IGF2). We tested the hypothesis that the common nonsynonymous genetic variants in M6P/IGF2R c.901C > G (Leu > Val) in exon 6 and c.5002G > A (Gly > Arg) in exon 34 are associated with risk of esophageal and gastric cancers. Study participants in this population-based study comprise 197 controls and 182 cases, including 105 with esophageal-gastric cardia adenocarcinoma (EGA), 57 with noncardia gastric adenocarcinoma and 20 with esophageal squamous (ES) cell carcinoma. Among white males, odds ratios (ORs) were elevated in relation to carrying at least 1 c.901C > G allele for EGA [OR = 1.9; 95% confidence intervals (CIs) = 1.0-3.6] and noncardia gastric cancer (OR = 2.5; 95% CI = 1.2-5.5), but not ES. Exploratory subgroup analyses suggested that associations between EGA and this variant were stronger among irregular or nonusers of nonsteroidal anti-inflammatory drugs (NSAIDs) (OR = 2.3; 95% CI = 1.2-4.2) and cigarette smokers (OR = 2.1; 95% CI = 1.0-4.2). An association between carrying the c.5002G > A genotype and EGA was not evident. These findings suggest that nonsynonymous polymorphisms in M6P/IGF2R may contribute to the risks of EGA and noncardia adenocarcinomas. Larger studies are required to confirm these findings.
authors.affiliation: Department of Community and Family Medicine, Duke University, Durham, NC 27710, USA. hoyo0001@mc.duke.edu
authors.forename: Cathrine
authors.initials: C
authors.lastname: Hoyo
authors.forename: Joellen M
authors.initials: JM
authors.lastname: Schildkraut
authors.forename: Susan K
authors.initials: SK
authors.lastname: Murphy
authors.forename: Wong-Ho
authors.initials: WH
authors.lastname: Chow
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Vaughan
authors.forename: Harvey
authors.initials: H
authors.lastname: Risch
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Marks
authors.forename: Randy L
authors.initials: RL
authors.lastname: Jirtle
authors.forename: Brian
authors.initials: B
authors.lastname: Calingaert
authors.forename: Brian
authors.initials: B
authors.lastname: Calingeart
authors.forename: Susan
authors.initials: S
authors.lastname: Mayne
authors.forename: Joseph
authors.initials: J
authors.lastname: Fraumeni
authors.forename: Marilie D
authors.initials: MD
authors.lastname: Gammon
mesh_terms: D000230:Adenocarcinoma / Q000453:epidemiology / Q000235:genetics* / Q000556:secondary; D000368:Aged; D016022:Case-Control Studies; D004938:Esophageal Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D017527:Receptor, IGF Type 2 / Q000235:genetics*; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D015996:Survival Rate
chemical_list: D017527:Receptor, IGF Type 2