title: Ala394Thr polymorphism in the clock gene NPAS2: a circadian modifier for the risk of non-Hodgkin's lymphoma.
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.
authors.affiliation: Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT 06520, USA. yong.zhu@yale.edu
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhu
authors.forename: Derek
authors.initials: D
authors.lastname: Leaderer
authors.forename: Carly
authors.initials: C
authors.lastname: Guss
authors.forename: Heather N
authors.initials: HN
authors.lastname: Brown
authors.forename: Yawei
authors.initials: Y
authors.lastname: Zhang
authors.forename: Peter
authors.initials: P
authors.lastname: Boyle
authors.forename: Richard G
authors.initials: RG
authors.lastname: Stevens
authors.forename: Aaron
authors.initials: A
authors.lastname: Hoffman
authors.forename: Qin
authors.initials: Q
authors.lastname: Qin
authors.forename: Xuesong
authors.initials: X
authors.lastname: Han
authors.forename: Tongzhang
authors.initials: T
authors.lastname: Zheng
mesh_terms: D000368:Aged; D000409:Alanine / Q000235:genetics; D019943:Amino Acid Substitution; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D056926:CLOCK Proteins; D002940:Circadian Rhythm / Q000235:genetics*; D003237:Connecticut / Q000453:epidemiology; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D005820:Genetic Testing; D006801:Humans; D016393:Lymphoma, B-Cell / Q000453:epidemiology*; D008228:Lymphoma, Non-Hodgkin / Q000453:epidemiology*; D008875:Middle Aged; D017720:Molecular Epidemiology; D009419:Nerve Tissue Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D011153:Population / Q000235:genetics; D012306:Risk; D013912:Threonine / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics
chemical_list: D000409:Alanine; D051792:Basic Helix-Loop-Helix Proteins; D056926:CLOCK Proteins; D009419:Nerve Tissue Proteins; D013912:Threonine; D015534:Trans-Activators; C104264:NPAS2 protein, human; C538943:CLOCK protein, human