Interleukin-10 promoter variants predict HPV-positive tumors and survival of squamous cell carcinoma of the oropharynx

FASEB J. 2013 Jun;27(6):2496-503. doi: 10.1096/fj.12-226803. Epub 2013 Feb 21.

Abstract

Interleukin-10 (IL-10) plays an important role in a host's defense against human papillomavirus (HPV) infection. IL-10 promoter variants may affect its expression level or functional efficiency and, subsequently, susceptibility to and survival of HPV16-associated squamous cell carcinoma of oropharynx (SCCOP). We determined tumor HPV16 DNA and genotyped three IL-10 promoter polymorphisms in 309 incident patients with SCCOP. Compared with the patients with corresponding common homozygous genotypes, patients carrying variant genotypes of IL-10 rs1800871 and rs1800872 were ~2.5 times more likely to have HPV16(+) tumors among patients with SCCOP. Among HPV16(+) patients with SCCOP only, compared to those with the corresponding variant genotypes, the patients with IL-10 rs1800871 and rs1800872 CC genotypes had significantly better survival and ~70-80% reduced risk of death/recurrence after multivariable adjustment. Additionally, functional relevance of these variants was characterized to explore the genotype-phenotype correlation. Our findings indicate that IL-10 genetic variants may be associated with tumor HPV16(+) SCCOP and predict survival of HPV16(+) patients with SCCOP. Larger studies are needed to validate our findings.

Keywords: HPV; IL-10 variants; biomarkers; oropharyngeal cancer; smoking; survival.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / immunology*
  • Carcinoma, Squamous Cell / virology
  • Female
  • Genetic Predisposition to Disease
  • Genetic Variation
  • Human papillomavirus 16 / isolation & purification
  • Human papillomavirus 16 / pathogenicity*
  • Humans
  • Interleukin-10 / blood
  • Interleukin-10 / genetics*
  • Male
  • Middle Aged
  • Oropharyngeal Neoplasms / genetics*
  • Oropharyngeal Neoplasms / immunology*
  • Oropharyngeal Neoplasms / virology
  • Papillomavirus Infections / complications
  • Papillomavirus Infections / genetics*
  • Papillomavirus Infections / immunology*
  • Polymorphism, Single Nucleotide
  • Promoter Regions, Genetic
  • Risk Factors
  • Survivors

Substances

  • IL10 protein, human
  • Interleukin-10