Document Type



Medicine and Health Sciences


Circadian genes have the potential to influence a variety of cancer-related biological pathways, including immune regulation, which may influence susceptibility to non-Hodgkin’s lymphoma (NHL). However, few studies have examined the role of circadian genes in lymphomagenesis. The current study examined Cryptochrome 2 (CRY2), a core circadian gene and transcriptional repressor, as a potential circadian biomarker for NHL. We first performed genetic association analyses of tagging SNPs in CRY2 and NHL risk using DNA samples from a population-based case-control study (N= 455 cases and 527 controls). Three SNPs were found to be significantly associated with risk of NHL when combining all subtypes (dbSNP IDs, odds ratios (ORs), and 95% confidence intervals: rs11038689, OR=2.34 (1.28-4.27), P=0.006; rs7123390, OR=2.40 (1.39-4.13), P=0.002; and rs1401417, OR=2.97 (1.57-5.63), P=0.001). Each of these associations remained significant when restricting the analysis to B-Cell cases and when further restricting to follicular lymphomas. An analysis of CRY2 diplotypes confirmed these significant findings. To further determine the functional impact of CRY2, we silenced the gene in vitro and performed a whole genome expression microarray. A pathway-based analysis showed that genes significantly altered by CRY2 knockdown formed networks associated with immune response and hematological system development. In addition, these genes were predicted to have significant impacts on several disease processes, including cancer (B-H P-value=3.75E-9) and hematological disease (B-H P=8.01E-8). In conclusion, both genetic association and functional analyses suggest that the circadian gene CRY2 may play an important role in NHL development.


Cancer Res. Author manuscript; available in PMC 2011 September 19. Published in final edited form as: Cancer Res. 2009 April 15; 69(8): 3605–3613. Published online 2009 March 24. doi: 10.1158/0008-5472.CAN-08-4572 PMCID: PMC3175639 NIHMSID: NIHMS318133