Research article

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

Soroush Nasri¹ , Helen More¹ , Francesco Graziano² , Annamaria Ruzzo³ , Emily Wilson⁴ , Anita Dunbier⁵ , Cushla McKinney⁶ , Tony Merriman⁶ , Parry Guilford¹ , Mauro Magnani³ and Bostjan Humar¹

¹  Cancer Genetics Laboratory, Department of Biochemistry, University of Otago, Dunedin 9054, Aotearoa New Zealand

²  Medical Oncology Unit, Azienda Ospedale "S. Salvatore", 61100 Pesaro, Italy

³  Institute of Biochemistry, University of Urbino, 61029 Urbino, Italy

⁴  Department of Molecular Medicine & Pathology, University of Auckland, Auckland 1142, Aotearoa, New Zealand

⁵  Institute of Cancer Research, London SW3 6JB, UK

⁶  Department of Biochemistry, University of Otago, Dunedin 9054, Aotearoa, New Zealand

author email corresponding author email

BMC Cancer 2008, 8:138doi:10.1186/1471-2407-8-138

Published:	15 May 2008

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 χ²-tests and logistic regression. The relative contribution of alleles was estimated by haplotype analysis.

Results

We 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.

Conclusion

The 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.