IGF2R polymorphisms and risk of esophageal and gastric adenocarcinomas.
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.
Hoyo
Cathrine
C
Department of Community and Family Medicine, Duke University, Durham, NC 27710, USA. hoyo0001@mc.duke.edu
Schildkraut
Joellen M
JM
Murphy
Susan K
SK
Chow
Wong-Ho
WH
Vaughan
Thomas L
TL
Risch
Harvey
H
Marks
Jeffrey R
JR
Jirtle
Randy L
RL
Calingaert
Brian
B
Calingeart
Brian
B
Mayne
Susan
S
Fraumeni
Joseph
J
Gammon
Marilie D
MD
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
D017527:Receptor, IGF Type 2