Combined p53-related genetic variants together with HPV infection increase oral cancer risk

• Published in: International journal of cancer Vol. 131; no. 3; pp. E251 - E258
• Main Authors: Wang, Zhongqiu, Sturgis, Erich M., Zhang, Yang, Huang, Zhigang, Zhou, Qi, Wei, Qingyi, Li, Guojun
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.08.2012; Wiley Subscription Services, Inc
• Subjects: Adult; Aged; Cancer; Case-Control Studies; Cell Cycle Proteins; Codons; DNA-Binding Proteins - genetics; Female; Genes, p53; Genetic diversity; Genetics; Genotype; Genotype & phenotype; Health risk assessment; HPV infection; Human papillomavirus; Human papillomavirus 16 - immunology; Humans; Male; MDM2; MDM2 protein; MDM4; Medical research; Middle Aged; Mouth Neoplasms - genetics; Mouth Neoplasms - pathology; Mouth Neoplasms - virology; Nuclear Proteins - genetics; Oral cancer; Oropharyngeal cancer; Oropharyngeal Neoplasms - genetics; p53; p53 Protein; p73; Papillomavirus Infections - genetics; Papillomavirus Infections - virology; Polymorphism; Polymorphism, Single Nucleotide; Promoter Regions, Genetic; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins c-mdm2 - genetics; Risk; Risk groups; Tumor Protein p73; Tumor Suppressor Proteins - genetics
• ISSN: 0020-7136; 1097-0215; 1097-0215
• DOI: 10.1002/ijc.27335

To explore the role of polymorphisms of p53‐related genes in etiology of oral cancer, we investigated joint effects of seven putatively functional polymorphisms of p53 (codon 72 Arg/Pro), p73 (4/14 GC/AT), murine double minute 2 gene (MDM2; A2164G and T2580G) and MDM4 (rs11801299 G > A, rs10900598 G > T and rs1380576 C > G) on risk of human papillomavirus (HPV)16‐associated oral cancer in a case–control study with 325 cases and 335 cancer‐free controls. We found that HPV16 seropositivity alone was associated with an increased risk of oral cancer [adjusted odds ratio (OR), 3.1; 95% confidence interval (CI), 2.1–4.6]. After combining genotypes of seven polymorphisms and using the low‐risk group (0–3 combined risk genotypes) and HPV16 seronegativity as the reference group, the medium‐risk (4 combined risk genotypes) and high‐risk groups (5–7 combined risk genotypes) and HPV16 seronegativity were associated with only an OR of 1.6 (95% CI, 1.1–2.5) and 1.2 (95% CI, 0.7–1.9) for oral cancer risk, respectively, whereas the low‐risk, medium‐risk and high‐risk groups and HPV16 seropositivity were significantly associated with a higher OR of 2.1 (95% CI, 1.2–3.6), 4.0 (95% CI, 1.8–9.1) and 19.1 (95% CI, 5.7–64.2), respectively. Notably, such effect modification by these combined risk genotypes was particularly pronounced in young subjects (aged < 50 years), never smokers and patients with oropharyngeal cancer. Taken together, these findings suggest that the combined risk genotypes of p53‐related genes may modify risk of HPV16‐associated oral cancer, especially in young patients, never‐smokers and patients with oropharyngeal cancer. Larger studies are needed to validate our findings.