Ala394Thr polymorphism in the clock gene NPAS2: a circadian modifier for the risk of non-Hodgkin's lymphoma.
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.
Zhu
Yong
Y
Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT 06520, USA. yong.zhu@yale.edu
Leaderer
Derek
D
Guss
Carly
C
Brown
Heather N
HN
Zhang
Yawei
Y
Boyle
Peter
P
Stevens
Richard G
RG
Hoffman
Aaron
A
Qin
Qin
Q
Han
Xuesong
X
Zheng
Tongzhang
T
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
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