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Keywords:

  • p73 polymorphism;
  • cancer risk;
  • genetic susceptibility;
  • human papillomavirus;
  • molecular epidemiology;
  • oropharynx;
  • squamous cell carcinoma

Abstract

BACKGROUND.

The p53 tumor suppressor protein homolog p73 can be inactivated by oncoprotein E6 of human papillomavirus (HPV). Variation in p73 may alter the interaction between the E6 protein and p73 and, thus, alter the risk for HPV-associated carcinogenesis. It is believed that the p73 G4C14-to-A4T14 polymorphism affects p73 function by altering gene expression; however, whether that polymorphism also alters the risk of HPV type 16 (HPV-16)-associated squamous cell carcinoma of the oropharynx (SCCOP) is unknown.

METHODS.

The current case-control study included a case group of 188 non-Hispanic white patients with newly diagnosed SCCOP and a control group of 349 healthy individuals. Logistic regression analyses were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for cases and controls stratified by p73 genotype, age, sex, smoking status, alcohol use, and HPV-16 status. The effects of p73 genotypes on the risk of HPV-16-associated SCCOP were explored with further stratification by smoking and drinking status.

RESULTS.

HPV-16 seropositivity was associated with an increased risk of SCCOP (adjusted OR, 5.98; 95% CI, 3.89-9.20), especially among never smokers (adjusted OR, 13.8; 95% CI, 5.91-32.1), never drinkers (adjusted OR, 14.9; 95% CI, 5.24-42.4), and individuals with p73 variant genotypes (GC/AT and AT/AT; adjusted OR, 7.96; 95% CI, 3.83-16.5). Moreover, the risk of HPV-16-associated SCCOP for individuals who had p73 variant genotypes was particularly high in never smokers and never drinkers.

CONCLUSIONS.

The p73 G4C14-to-A4T14 polymorphism may modulate the risk of HPV-16-associated SCCOP, and the p73 variant genotypes may be markers of genetic susceptibility to HPV-16-associated SCCOP, particularly in never smokers and never drinkers. Cancer 2008. © 2008 American Cancer Society.