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Background  The purpose of this study is to analyze the combined effects of selected  p 53 and  p 73 polymorphisms and their interaction with lifestyle habits on squamous cell carcinoma of the head and neck (SCCHN) risk and progression in an Italian population.    Methods  Two hundred and eighty-three cases and 295 hospital controls were genotyped for  p 53 polymorphisms on exon 4 (Arg72Pro), intron 3 and 6, and  p 73 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  p 53 polymorphisms, and a gene-gene interaction analysis for the combined effects of  p 73 G4C14-to-A4T14 and  p 53 polymorphisms.    Results  We found a significant increased risk of SCCHN among individuals with combined  p 73 exon 2 G4A and  p 53 intron 3 variant alleles (OR = 2.22, 95% CI: 1.08–4.56), and a protective effect for those carrying the  p 53 exon 4- p 53 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  p 73 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  p 53 intron 6 variant allele carriers (Hazard Ratio = 0.51 (95% CI: 0.23–1.16).    Conclusion  Our study provides for the first time evidence that individuals carrying  p 53 exon 4 and  p 53 intron 6 variant alleles are significantly protected against SCCHN, and also shows that an additional risk is conferred by the combination of  p 73 exon 2 G4C14-to-A4T14 and  p 53 intron 3 variant allele. Larger studies are required to confirm these findings.

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