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.
Highlights
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
Results show that alcohol consumption increases head and neck cancer risk, especially among heavy drinkers (OR = 18.56; 95% confidence intervals (CI): 7.26–47.44)
An increased risk was detected for cigarette smokers, with an Odds Ratio (OR) of 2.97 and 8.23 for 1–24 and > 24 pack-years of cigarettes smoked, respectively (Table 1)
Summary
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. Some studies reported that rare p53 exon 4 – intron 3 – intron 6 haplotypes affect the frequency of mutation and loss of heterozygosity in B-lymphoblastoid cell lines, along with DNA repair and apoptosis [11,12]. P53 exon 4 Arg72Pro polymorphism is the only p53 single nucleotide polymorphism (SNP) whose effect has been studied in relation to SCCHN, with conflicting results. Three studies conducted on Caucasians [13,14,15] reported the absence of a significant relationship between Pro variant allele and SCCHN, while Tsai et al [16] suggested an increased cancer risk for individuals carrying the variant allele in a Chinese population. No one study far has investigated the effect of these two SNPs on SCCHN
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