Cytokines and tumor metastasis gene variants in oral cancer and precancer in Puerto Rico

PLoS One. 2013 Nov 20;8(11):e79187. doi: 10.1371/journal.pone.0079187. eCollection 2013.

Abstract

Objectives: A cross-sectional epidemiological study explored genetic susceptibility to oral precancer and cancer in Puerto Rico (PR).

Materials and methods: Three hundred three individuals with a benign oral condition, oral precancer (oral epithelial hyperplasia/hyperkeratosis, oral epithelial dysplasia), or oral squamous cell carcinoma (SCCA) were identified via PR pathology laboratories. A standardized, structured questionnaire obtained information on epidemiological variables; buccal cells were collected for genetic analysis. Genotyping was performed using Taqman® assays. Allelic frequencies of single nucleotide polymorphisms (SNPs) were evaluated in cytokine genes and genes influencing tumor metastasis. Risk estimates for a diagnosis of oral precancer or SCCA while having a variant allele were generated using logistic regression. Adjusted models controlled for age, gender, ancestry, education, smoking and alcohol consumption.

Results: Relative to persons with a benign oral lesion, individuals with homozygous recessive allelic variants of tumor necrosis factor (TNF-α) -238 A/G SNP had a reduced odds of having an oral precancer (ORadjusted = 0.15; 95% CI 0.03-0.70). The transforming growth factor beta-1 (TGFβ-1 -509 C/T) polymorphism was inversely associated with having an oral SCCA among persons homozygous for the recessive variant (ORcrude = 0.27; 95% CI 0.09-0.79). The matrix metalloproteinase gene (MMP-1) variant, rs5854, was associated with oral SCCA; participants with even one variant allele were more likely to have oral SCCA (ORadjusted = 2.62, 95% CI 1.05-6.53) compared to people with ancestral alleles.

Conclusion: Our exploratory analyses suggest that genetic alterations in immune system genes and genes with metastatic potential are associated with oral precancer and SCCA risk in PR.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Female
  • Gene Frequency / genetics
  • Genetic Predisposition to Disease / genetics
  • Genotype
  • Humans
  • Interleukin-10 / genetics
  • Interleukin-1beta / genetics
  • Logistic Models
  • Male
  • Middle Aged
  • Mouth Mucosa / metabolism
  • Mouth Mucosa / pathology
  • Mouth Neoplasms / genetics*
  • Mouth Neoplasms / metabolism*
  • Polymorphism, Single Nucleotide / genetics
  • Puerto Rico

Substances

  • Interleukin-1beta
  • Interleukin-10