Zhu Yong, Leaderer Derek, Guss Carly, Brown Heather N, Zhang Yawei, Boyle Peter, Stevens Richard G, Hoffman Aaron, Qin Qin, Han Xuesong, Zheng Tongzhang
Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT 06520, USA.
Int J Cancer. 2007 Jan 15;120(2):432-5. doi: 10.1002/ijc.22321.
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.
昼夜节律紊乱被认为会导致免疫失调，而免疫失调是唯一已确定的非霍奇金淋巴瘤（NHL）风险因素。负责昼夜节律的基因也作为潜在的肿瘤抑制因子参与癌症相关的生物学途径。然而，以前没有研究探讨过昼夜节律基因与NHL风险之间的关联。在这项基于人群的病例对照研究中（455例病例；527例对照），我们检测了最大的昼夜节律基因神经元PAS结构域蛋白2（NPAS2）中唯一已确定的非同义多态性（Ala394Thr；rs2305160），以研究其对NHL风险的影响。我们的结果表明，变异的苏氨酸基因型（Ala/Thr和Thr/Thr）与降低的NHL风险显著相关（比值比=0.66，95%置信区间：0.51-0.85，p=0.001），尤其是B细胞淋巴瘤（比值比=0.61，95%置信区间：0.47-0.80，p≤0.0001）。这些发现提供了首个分子流行病学证据，支持昼夜节律基因在淋巴瘤发生中的作用，这表明昼夜节律基因的遗传变异可能是一组用于NHL的有前景的新型生物标志物，值得进一步研究。
