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A novel diffuse gastric cancer susceptibility variant in E-cadherin (CDH1) intron 2: A case control study in an Italian population

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Date
2008-05
ICR Author
McKinney, Cushla
Type
Journal Article
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Abstract
Background: Inherited genetic factors such as E-cadherin (CDH1) promoter variants are believed to influence the risk towards sporadic diffuse gastric cancer (DGC). Recently, a new regulatory region essential for CDH1 transcription has been identified in CDH1 intron 2. Methods: We genotyped all known polymorphisms located within conserved sequences of CDH1 intron 2 ( rs10673765, rs9932686, rs1125557, rs9282650, rs9931853) in an Italian population consisting of 134 DGC cases and 100 healthy controls ( 55 patient relatives and 45 unrelated, matched individuals). The influence of individual variants on DGC risk was assessed using.2- tests and logistic regression. The relative contribution of alleles was estimated by haplotype analysis. Results: We observed a significant ( p \ensuremath< 0.0004) association of the CDH1 163+ 37235G \ensuremath> A variant ( rs1125557) with DGC risk. Odds ratios were 4.55 ( 95% Cl = 2.09-9.93) and 1.38 ( 95% Cl = 0.75-2.55) for AA and GA carriers, respectively. When adjusted for age, sex, smoking status, alcohol intake and H. pylori infection, the risk estimates remained largely significant for AA carriers. Haplotype analysis suggested the 163+ 37235A- allele contributes to disease risk independently of the other variants studied. Conclusion: The CDH1 163+ 37235G \ensuremath> A polymorphism may represent a novel susceptibility variant for sporadic DGC if confirmed in other populations. Considering the broad expression of E-cadherin in epithelia, this exploratory study encourages further evaluation of the 163+ 37235A-allele as a susceptibility variant in other carcinomas.
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https://repository.icr.ac.uk/handle/internal/1805
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  • Other ICR Research
Language
eng
License start date
2008-05
Citation
BMC CANCER, 2008, 8

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