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


METHODS
Two 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.


RESULTS
We 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).


CONCLUSIONS
Our 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.
Gallì
Paola
P
Institute of Hygiene Università Cattolica del Sacro Cuore, Rome, Italy. paola.galli@edu.rm.unicatt.it
Cadoni
Gabriella
G
Volante
Mariangela
M
De Feo
Emma
E
Amore
Rosarita
R
Giorgio
Arianna
A
Arzani
Dario
D
Paludetti
Gaetano
G
Ricciardi
Gualtiero
G
Boccia
Stefania
S
D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D016022:Case-Control Studies; D004268:DNA-Binding Proteins / Q000235:genetics*; D005091:Exons; D005260:Female; D020022:Genetic Predisposition to Disease; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006801:Humans; D007438:Introns; D007558:Italy; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D044465:White People / Q000235:genetics*
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins