Ala394Thr polymorphism in the clock gene NPAS2: a circadian modifier for the risk of non-Hodgkin's lymphoma

Int J Cancer. 2007 Jan 15;120(2):432-5. doi: 10.1002/ijc.22321.

Abstract

Circadian disruption is theorized to cause immune dysregulation, which is the only established risk factor for non-Hodgkin's lymphoma (NHL). Genes responsible for circadian rhythm are also involved in cancer-related biological pathways as potential tumor suppressors. However, no previous studies have examined associations between circadian genes and NHL risk. In this population-based case control study (n = 455 cases; 527 controls), we examined the only identified nonsynonymous polymorphism (Ala394Thr; rs2305160) in the largest circadian gene, neuronal PAS domain protein 2 (NPAS2), in order to examine its impact on NHL risk. Our results demonstrate a robust association of the variant Thr genotypes (Ala/Thr and Thr/Thr) with reduced risk of NHL (OR = 0.66, 95% CI: 0.51-0.85, p = 0.001), especially B-cell lymphoma (OR = 0.61, 95% CI: 0.47-0.80, p <or= 0.0001). These findings provide the first molecular epidemiologic evidence supporting a role of circadian genes in lymphomagenesis, which suggests that genetic variations in circadian genes might be a novel panel of promising biomarkers for NHL and warrants further investigation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alanine / genetics
  • Amino Acid Substitution
  • Basic Helix-Loop-Helix Transcription Factors / genetics*
  • CLOCK Proteins
  • Circadian Rhythm / genetics*
  • Connecticut / epidemiology
  • Female
  • Genetic Predisposition to Disease / epidemiology*
  • Genetic Testing
  • Humans
  • Lymphoma, B-Cell / epidemiology*
  • Lymphoma, Non-Hodgkin / epidemiology*
  • Middle Aged
  • Molecular Epidemiology
  • Nerve Tissue Proteins / genetics*
  • Polymorphism, Genetic*
  • Population / genetics
  • Risk
  • Threonine / genetics
  • Trans-Activators / genetics

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • NPAS2 protein, human
  • Nerve Tissue Proteins
  • Trans-Activators
  • Threonine
  • CLOCK Proteins
  • CLOCK protein, human
  • Alanine