A case-control study on the combined effects of p53 and p73 polymorphisms on head and neck cancer risk in an Italian populationReportar como inadecuado




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BMC Cancer

, 9:137

First Online: 08 May 2009Received: 23 July 2008Accepted: 08 May 2009DOI: 10.1186-1471-2407-9-137

Cite this article as: Gallì, P., Cadoni, G., Volante, M. et al. BMC Cancer 2009 9: 137. doi:10.1186-1471-2407-9-137

Abstract

BackgroundThe purpose of this study is to analyze the combined effects of selected p53 and p73 polymorphisms and their interaction with lifestyle habits on squamous cell carcinoma of the head and neck SCCHN risk and progression in an Italian population.

MethodsTwo hundred and eighty-three cases and 295 hospital controls were genotyped for p53 polymorphisms on exon 4 Arg72Pro, intron 3 and 6, and p73 G4C14-to-A4T14. Their association with SCCHN was estimated using a logistic regression analysis, while a multinomial logistic regression approach was applied to calculate the effect of the selected polymorphisms on SCCHN different sites oral cavity, oropharynx, hypopharynx and larynx. We performed an haplotype analysis of the p53 polymorphisms, and a gene-gene interaction analysis for the combined effects of p73 G4C14-to-A4T14 and p53 polymorphisms.

ResultsWe found a significant increased risk of SCCHN among individuals with combined p73 exon 2 G4A and p53 intron 3 variant alleles OR = 2.22, 95% CI: 1.08–4.56, and a protective effect for those carrying the p53 exon 4-p53 intron 6 diplotype combination OR = 0.67; 95% CI: 0.47–0.92. From the gene-environment interaction analysis we found that individuals aged < 45 years carrying p73 exon 2 G4A variant allele have a 12.85-increased risk of SCCHN 95% CI: 2.10–78.74 compared with persons of the same age with the homozygous wild type genotype. Improved survival rate was observed among p53 intron 6 variant allele carriers Hazard Ratio = 0.51 95% CI: 0.23–1.16.

ConclusionOur study provides for the first time evidence that individuals carrying p53 exon 4 and p53 intron 6 variant alleles are significantly protected against SCCHN, and also shows that an additional risk is conferred by the combination of p73 exon 2 G4C14-to-A4T14 and p53 intron 3 variant allele. Larger studies are required to confirm these findings.

AbbreviationsCIConfidence Interval

DFSDisease Free Survival

HRHazard Ratio

HWEHardy-Weinberg Equilibrium

OROdds Ratio

PCRPolymerase Chain Reaction

SCCHNSquamous Cell Carcinoma of the Head and Neck

SNPSingle Nucleotide Polymorphism.

FDRFalse Discovery Rate.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2407-9-137 contains supplementary material, which is available to authorized users.

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Autor: Paola Gallì - Gabriella Cadoni - Mariangela Volante - Emma De Feo - Rosarita Amore - Arianna Giorgio - Dario Arzani - Gaet

Fuente: https://link.springer.com/







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