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Open Access Highly Accessed Research article

A case–control study on the effect of Apolipoprotein E genotypes on gastric cancer risk and progression

Emma De Feo1, Benedetto Simone1, Roberto Persiani2, Ferdinando Cananzi2, Alberto Biondi2, Dario Arzani1, Rosarita Amore1, Domenico D’Ugo2, Gualtiero Ricciardi1 and Stefania Boccia13*

Author affiliations

1 Institute of Hygiene, Università Cattolica del Sacro Cuore, Rome, Italy

2 Department of Surgery, Università Cattolica del Sacro Cuore, Rome, Italy

3 IRCCS San Raffaele Pisana, Rome, Italy

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Citation and License

BMC Cancer 2012, 12:494  doi:10.1186/1471-2407-12-494

Published: 25 October 2012

Abstract

Background

Apolipoprotein E (ApoE) is a multifunctional protein playing both a key role in the metabolism of cholesterol and triglycerides, and in tissue repair and inflammation. The ApoE gene (19q13.2) has three major isoforms encoded by ε2, ε3 and ε4 alleles with the ε4 allele associated with hypercholesterolemia and the ε2 allele with the opposite effect. An inverse relationship between cholesterol levels and gastric cancer (GC) has been previously reported, although the relationship between apoE genotypes and GC has not been explored so far.

Methods

One hundred and fifty-six gastric cancer cases and 444 hospital controls were genotyped for apoE polymorphism (ε2, ε3, ε4 alleles). The relationship between GC and putative risk factors was measured using the adjusted odds ratios (ORs) and their 95% confidence intervals (CIs) from logistic regression analysis. A gene-environment interaction analysis was performed. The effect of the apoE genotypes on survival from GC was explored by a Kaplan–Meier analysis and Cox proportional hazard regression model.

Results

Subjects carrying at least one apoE ε2 allele have a significant 60% decrease of GC risk (OR=0.40, 95% CI: 0.19 – 0.84) compared with ε3 homozygotes. No significant interaction emerged between the ε4 or ε2 allele and environmental exposures, nor ε2 or ε4 alleles affected the median survival times, even after correcting for age, gender and stadium.

Conclusions

Our study reports for the first time a protective effect of the ε2 allele against GC, that might be partly attributed to the higher antioxidant properties of ε2 compared with the ε3 or ε4 alleles. Given the study’s sample size, further studies are required to confirm our findings.

Keywords:
Gastric cancer; Apolipoprotein E; Genetic epidemiology; Polymorphism; Gene-environment interaction