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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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 </=</= 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. (c) 2006 Wiley-Liss, Inc.[1]


  1. Ala394Thr polymorphism in the clock gene NPAS2: A circadian modifier for the risk of non-Hodgkin's lymphoma. Zhu, Y., Leaderer, D., Guss, C., Brown, H.N., Zhang, Y., Boyle, P., Stevens, R.G., Hoffman, A., Qin, Q., Han, X., Zheng, T. Int. J. Cancer (2007) [Pubmed]
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