Association of a p73 exon 2 G4C14-to-A4T14 polymorphism with risk of squamous cell carcinoma of the head and neck.

p73, a novel p53 homolog, has some p53-like activity and plays an important role in modulating cell-cycle control, apoptosis and cell growth. p73 regulates differentiation of head and neck squamous epithelium, and changes in p73 may lead to the development of squamous cell carcinoma of the head and neck (SCCHN). Two linked non-coding exon 2 polymorphisms (designated as G4C14-to-A4T14) were identified recently but their functional relevance is unknown. We hypothesized that this p73 polymorphism plays a role in the etiology of SCCHN. Therefore, in this hospital-based case-control study of 708 patients newly diagnosed with SCCHN and 1229 cancer-free controls, we evaluated the association between the p73 AT variant allele and risk of SCCHN. The controls were frequency-matched to the cases by age (+/-5 years), sex and smoking status, and all subjects were non-Hispanic whites. Our results showed that the frequencies of variant AT allele and genotypes were more common in the cases than in the controls (P = 0.029 and P = 0.009, respectively). Compared with the GC/GC genotype, the variant genotypes (GC/AT + AT/AT) were associated with a statistically significantly increased risk for SCCHN [odds ratio (OR) = 1.33, 95% confidence interval (CI) = 1.10-1.60]. Further stratification analyses by age, sex, smoking and alcohol status and by cancer sites within the head and neck region indicated that this significantly increased risk was more pronounced in younger (< or =50 years) individuals (adjusted OR = 1.70; 95% CI, 1.19-2.43), women (1.61; 1.09-2.37), current smokers (1.77; 1.25-2.51) and patients with oral cancer (1.54; 1.15-2.07). Our results suggest that this p73 polymorphism may be a risk marker for genetic susceptibility to SCCHN.