NDLI: Circadian pathway genes in relation to glioma risk and outcome

Content Provider	Springer Nature Link
Author	Madden, Melissa H. Anic, Gabriella M. Thompson, Reid C. Nabors, L. Burton Olson, Jeffrey J. Browning, James E. Monteiro, Alvaro N. Egan, Kathleen M.
Copyright Year	2013
Abstract	There is growing evidence that circadian disruption may alter risk and aggressiveness of cancer. We evaluated common genetic variants in the circadian gene pathway for associations with glioma risk and patient outcome in a US clinic-based case–control study.Subjects were genotyped for 17 candidate single nucleotide polymorphisms in ARNTL, CRY1, CRY2, CSNK1E, KLHL30, NPAS2, PER1, PER3, CLOCK, and MYRIP. Unconditional logistic regression was used to estimate age and gender-adjusted odds ratios (OR) and 95 % confidence intervals (CI) for glioma risk under three inheritance models (additive, dominant, and recessive). Proportional hazards regression was used to estimate hazard ratios for glioma-related death among 441 patients with high-grade tumors. Survival associations were validated using The Cancer Genome Atlas (TCGA) dataset.A variant in PER1 (rs2289591) was significantly associated with overall glioma risk (per variant allele OR 0.80; 95 % CI 0.66–0.97; p trend = 0.027). The variant allele for CLOCK rs11133391 under a recessive model increased risk of oligodendroglioma (OR 2.41; 95 % CI 1.31–4.42; p = 0.005), though not other glioma subtypes (p for heterogeneity = 0.0033). The association remained significant after false discovery rate adjustment (p = 0.008). Differential associations by gender were observed for MYRIP rs6599077 and CSNK1E rs1534891 though differences were not significant after adjustment for multiple testing. No consistent mortality associations were identified. Several of the examined genes exhibited differential expression in glioblastoma multiforme versus normal brain in TCGA data (MYRIP, ARNTL, CRY1, KLHL30, PER1, CLOCK, and PER3), and expression of NPAS2 was significantly associated with a poor patient outcome in TCGA patients.This exploratory analysis provides some evidence supporting a role for circadian genes in the onset of glioma and possibly the outcome of glioma.
Starting Page	25
Ending Page	32
Page Count	8
File Format	PDF
ISSN	09575243
Journal	Cancer Causes & Control
Volume Number	25
Issue Number	1
e-ISSN	15737225
Language	English
Publisher	Springer Netherlands
Publisher Date	2013-10-18
Publisher Place	Dordrecht
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Glioma Single nucleotide polymorphism Genotype Cancer Research Biomedicine general Oncology Public Health Epidemiology Hematology
Content Type	Text
Resource Type	Article
Subject	Cancer Research Oncology

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