Abstract
BackgroundInherited 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.MethodsWe 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 χ2-tests and logistic regression. The relative contribution of alleles was estimated by haplotype analysis.ResultsWe observed a significant (p < 0.0004) association of the CDH1 163+37235G>A variant (rs1125557) with DGC risk. Odds ratios were 4.55 (95%CI = 2.09–9.93) and 1.38 (95%CI = 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.ConclusionThe CDH1 163+37235G>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.
Highlights
Inherited genetic factors such as E-cadherin (CDH1) promoter variants are believed to influence the risk towards sporadic diffuse gastric cancer (DGC)
(rs9282650), and 163+49526C>G), no additional common polymorphisms specific for the Italian population under study were discovered by Single-strand conformation polymorphism (SSCP) in the six regions
Our present results suggest a role of CDH1 intron 2 alleles in the risk of developing sporadic DGC and identify the 163+37235G>A single nucleotide polymorphism (SNP) as a putative susceptibility variant
Summary
Inherited genetic factors such as E-cadherin (CDH1) promoter variants are believed to influence the risk towards sporadic diffuse gastric cancer (DGC). The general incidence rates for stomach cancer are in a steady decline, largely due to decreasing rates of the intestinal cancer-type. This falling frequency is believed to be the result of improved nutrition and sanitary conditions. The incidence of diffuse gastric cancer (DGC) alone appears more stable over the past few decades [1,2]. Such a constant rate suggests a larger contribution of inherited genetic risk rather than environmental factors to the diffuse form of stomach cancer. Genetic DGC markers may facilitate the identification of individuals at risk and thereby contribute to an improvement in DGC diagnosis and therapy
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