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

Emma De Feo, Benedetto Simone, Roberto Persiani, Ferdinando Cananzi, Alberto Biondi, Dario Arzani, Rosarita Amore, Domenico D'Ugo, Gualtiero Ricciardi, Stefania Boccia

Research output: Contribution to journalArticle

21 Citations (Scopus)

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.

Original languageEnglish
Article number494
JournalBMC Cancer
Volume12
DOIs
Publication statusPublished - Oct 25 2012

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Apolipoproteins E
Stomach Neoplasms
Case-Control Studies
Alleles
Genotype
Odds Ratio
Cholesterol
Confidence Intervals
Gene-Environment Interaction
Environmental Exposure
Homozygote
Kaplan-Meier Estimate
Hypercholesterolemia
Proportional Hazards Models
Sample Size
Protein Isoforms
Triglycerides
Antioxidants
Logistic Models
Regression Analysis

Keywords

  • Apolipoprotein E
  • Gastric cancer
  • Gene-environment interaction
  • Genetic epidemiology
  • Polymorphism

ASJC Scopus subject areas

  • Oncology
  • Cancer Research
  • Genetics
  • Medicine(all)

Cite this

A case-control study on the effect of Apolipoprotein E genotypes on gastric cancer risk and progression. / De Feo, Emma; Simone, Benedetto; Persiani, Roberto; Cananzi, Ferdinando; Biondi, Alberto; Arzani, Dario; Amore, Rosarita; D'Ugo, Domenico; Ricciardi, Gualtiero; Boccia, Stefania.

In: BMC Cancer, Vol. 12, 494, 25.10.2012.

Research output: Contribution to journalArticle

De Feo, Emma ; Simone, Benedetto ; Persiani, Roberto ; Cananzi, Ferdinando ; Biondi, Alberto ; Arzani, Dario ; Amore, Rosarita ; D'Ugo, Domenico ; Ricciardi, Gualtiero ; Boccia, Stefania. / A case-control study on the effect of Apolipoprotein E genotypes on gastric cancer risk and progression. In: BMC Cancer. 2012 ; Vol. 12.
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title = "A case-control study on the effect of Apolipoprotein E genotypes on gastric cancer risk and progression",
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 = "Apolipoprotein E, Gastric cancer, Gene-environment interaction, Genetic epidemiology, Polymorphism",
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T1 - A case-control study on the effect of Apolipoprotein E genotypes on gastric cancer risk and progression

AU - De Feo, Emma

AU - Simone, Benedetto

AU - Persiani, Roberto

AU - Cananzi, Ferdinando

AU - Biondi, Alberto

AU - Arzani, Dario

AU - Amore, Rosarita

AU - D'Ugo, Domenico

AU - Ricciardi, Gualtiero

AU - Boccia, Stefania

PY - 2012/10/25

Y1 - 2012/10/25

N2 - 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.

AB - 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.

KW - Apolipoprotein E

KW - Gastric cancer

KW - Gene-environment interaction

KW - Genetic epidemiology

KW - Polymorphism

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