MicroRNA-related genetic variations as predictors for risk of second primary tumor and/or recurrence in patients with early-stage head and neck cancer

Carcinogenesis. 2010 Dec;31(12):2118-23. doi: 10.1093/carcin/bgq177. Epub 2010 Sep 5.

Abstract

Second primary tumor (SPT) and/or recurrence negatively impact the prognosis of patients with curatively treated early-stage head and neck cancer. MicroRNAs (miRNAs) play important roles in cancer development. We explored whether the variations of miRNA-related pathway were associated with the risk of SPT/recurrence in patients with early-stage head and neck cancer. This study includes 150 early-stage head and neck cancer patients with SPT/recurrence and 300 patients without SPT/recurrence. Two hundred and thirty-five tagging and potentially functional single-nucleotide polymorphisms (SNPs) were genotyped from eight miRNA biogenesis pathway genes and 135 miRNA-targeted genes. Eighteen miRNA-related SNPs were significantly associated with the risk of SPT/recurrence. The most significant SNP was rs3747238, a miRNA-binding site SNP in SMC1B. The variant homozygous genotype of this SNP was associated with a 1.74-fold increased risk [95% confidence interval (CI) 1.19-2.54; P = 0.004]. Cumulative effect analysis showed joint effects for the number of unfavorable genotype in patients. Survival tree analysis further identified the high-order gene-gene interactions and categorized the study subjects into low-, medium- and high-risk groups. Patients in the high-risk group had a 4.84-fold increased risk (95% CI: 3.11-7.51; P = 2.45 × 10(-12)) and a shorter event-free median survival time of 37.9 months (log rank P = 2.28 × 10(-13)). Our results suggested that miRNA-related genetic polymorphisms may be used individually and jointly to predict the risk of SPT/recurrence of early-stage head and neck cancer patients.

Publication types

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

MeSH terms

  • Cell Cycle Proteins / genetics
  • Chromosomal Proteins, Non-Histone / genetics
  • Genetic Variation
  • Genotype
  • Head and Neck Neoplasms / etiology
  • Head and Neck Neoplasms / genetics*
  • Head and Neck Neoplasms / pathology
  • Humans
  • Karyopherins / genetics
  • MicroRNAs / physiology*
  • Neoplasm Recurrence, Local / etiology
  • Neoplasm Recurrence, Local / genetics*
  • Neoplasm Staging
  • Neoplasms, Second Primary / etiology
  • Neoplasms, Second Primary / genetics*
  • Polymorphism, Single Nucleotide*
  • Risk

Substances

  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • Karyopherins
  • MicroRNAs
  • XPO5 protein, human
  • structural maintenance of chromosome protein 1