A case-control study on the effect of p53 and p73 gene polymorphisms on gastric cancer risk and progression

Emma De Feo, Roberto Persiani, Antonio La Greca, Rosarita Amore, Dario Arzani, Stefano Rausei, Domenico D'Ugo, Paolo Magistrelli, Cornelia M. van Duijn, Gualtiero Ricciardi, Stefania Boccia

Research output: Contribution to journalArticlepeer-review

Abstract

The p53 protein and its functional homologue p73 share several functions in modulating cell-cycle control and apoptosis. Based on the functional interaction between p53 and p73 in carcinogenesis, we investigated the combined effect of p73 G4C14-to-A4T14 and p53 gene polymorphisms and their interaction with selected environmental factors, on the risk for gastric cancer in a hospital-based case-control study conducted in Italy. The effect of these polymorphisms on cancer progression was also investigated. One hundred and fifteen gastric cancer cases and 295 hospital controls were genotyped for p73 G4C14-to-A4T14, and p53 exon 4 (Arg72Pro), intron 3 and intron 6 polymorphisms. An increased risk for gastric cancer was found to be associated with the inheritance of the p73 homozygous variant genotype among the gastric cancer intestinal histotype (odds ratio (OR) = 6.75; 95% confidence interval (95% CI) = 1.88-24.24). An effect modification of the p73 variant allele by gender was observed [(OR = 2.82; 95%CI = 1.24-6.40) among females, versus an OR of 0.70 (95%CI = 0.32-1.54) among males; p-value for homogeneity among strata estimates =0.03]. Gene-gene interaction analyses demonstrated that individuals with combined p53 exon 4 and intron 6 variant alleles are borderline significantly protected from gastric cancer (OR = 0.52; 95% CI = 0.26-1.07; p-value for interaction =0.005), which was confirmed by the haplotype analysis. Finally, a poorer survival was observed among carriers of the variant allele of p53 intron 6 if compared with those carrying both wild-type alleles (p-value for log-rank test =0.02). This study shows that the p73 G4C14-to-A4T14 polymorphism may be a risk factor for gastric cancer, as reported from other studies in different tumour sites among Caucasians. Along with the protective effect of p53 exon 4-intron 6 allelic variants, already noted for breast and lung cancer, our results require confirmation from larger studies.

Original languageEnglish
Pages (from-to)60-65
Number of pages6
JournalMutation Research - Genetic Toxicology and Environmental Mutagenesis
Volume675
Issue number1-2
DOIs
Publication statusPublished - Apr 30 2009

Keywords

  • Gastric cancer
  • Genetic epidemiology
  • Haplotype
  • p53
  • p73
  • Single nucleotide polymorphisms

ASJC Scopus subject areas

  • Health, Toxicology and Mutagenesis
  • Genetics

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