NAD(P)H: quinone oxidoreductase 1 and NRH:quinone oxidoreductase 2 polymorphisms in papillary thyroid microcarcinoma: correlation with phenotype

Yonsei Med J. 2013 Sep;54(5):1158-67. doi: 10.3349/ymj.2013.54.5.1158.

Abstract

Purpose: NAD(P)H:Quinone Oxidoreductase 1 (NQO1) C609T missense variant (NQO1*2) and 29 basepair (bp)-insertion/deletion (I29/D) polymorphism of the NRH:Quinone Oxidoreductase 2 (NQO2) gene promoter have been proposed as predictive and prognostic factors for cancer development and progression. The purpose of this study is to investigate the relationship between NQO1/NQO2 genotype and clinico-pathological features of papillary thyroid microcarcinoma (PTMC).

Materials and methods: Genomic DNA was isolated from 243 patients; and clinical data were retrospectively analyzed. NQO1*2 and tri-allelic polymorphism of NQO2 were investigated by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis.

Results: PTMC with NQO1*2 frequently exhibited extra-thyroidal extension as compared to PTMC with wild-type NQO1 (p=0.039). There was a significant relationship between I29/I29 homozygosity of NQO2 and lymph node metastasis (p=0.042). Multivariate analysis showed that the I29/I29 genotype was associated with an increased risk of lymph node metastasis (OR, 2.24; 95% CI, 1.10-4.56; p=0.026).

Conclusion: NQO1*2 and I29 allele of the NQO2 are associated with aggressive clinical phenotypes of PTMC, and the I29 allele represents a putative prognostic marker for PTMC.

Keywords: NAD(P)H:Quinone Oxidoreductase 1; NRH:Quinone Oxidoreductase 2; thyroid neoplasm.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Carcinoma, Papillary / genetics*
  • Carcinoma, Papillary / pathology
  • DNA Mutational Analysis
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Mutagenesis, Insertional
  • Mutation, Missense
  • NAD(P)H Dehydrogenase (Quinone) / chemistry
  • NAD(P)H Dehydrogenase (Quinone) / genetics*
  • Phenotype
  • Polymorphism, Genetic
  • Prognosis
  • Promoter Regions, Genetic
  • Retrospective Studies
  • Sequence Analysis, Protein
  • Sequence Deletion
  • Thyroid Neoplasms / genetics*
  • Thyroid Neoplasms / pathology

Substances

  • NAD(P)H Dehydrogenase (Quinone)
  • NQO1 protein, human

Supplementary concepts

  • Papillary Thyroid Microcarcinoma