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

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 epsilon 2, epsilon 3 and epsilon 4 alleles with the epsilon 4 allele associated with hypercholesterolemia and the epsilon 2 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 (epsilon 2, epsilon 3, epsilon 4 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 epsilon 2 allele have a significant 60% decrease of GC risk (OR=0.40, 95% CI: 0.19-0.84) compared with epsilon 3 homozygotes. No significant interaction emerged between the epsilon 4 or epsilon 2 allele and environmental exposures, nor epsilon 2 or epsilon 4 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 epsilon 2 allele against GC, that might be partly attributed to the higher antioxidant properties of epsilon 2 compared with the epsilon 3 or epsilon 4 alleles. Given the study's sample size, further studies are required to confirm our findings.