PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: This exploratory analysis provides some evidence supporting a role for circadian genes in the onset of glioma and possibly the outcome of glioma.
PURPOSE: 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. METHODS: 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. RESULTS: 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 CLOCKrs11133391 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 MYRIPrs6599077 and CSNK1Ers1534891 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. CONCLUSION: This exploratory analysis provides some evidence supporting a role for circadian genes in the onset of glioma and possibly the outcome of glioma.
Authors: Kathleen M Egan; Reid C Thompson; L B Nabors; Jeffrey J Olson; Daniel J Brat; Renato V Larocca; Steven Brem; Paul L Moots; Melissa H Madden; James E Browning; Y Ann Chen Journal: J Neurooncol Date: 2011-01-04 Impact factor: 4.130
Authors: Michelle Luciano; Narelle K Hansell; Jari Lahti; Gail Davies; Sarah E Medland; Katri Räikkönen; Albert Tenesa; Elisabeth Widen; Kevin A McGhee; Aarno Palotie; David Liewald; David J Porteous; John M Starr; Grant W Montgomery; Nicholas G Martin; Johan G Eriksson; Margaret J Wright; Ian J Deary Journal: Biol Psychol Date: 2010-12-03 Impact factor: 3.251
Authors: Marta Garaulet; Carmen Sánchez-Moreno; Caren E Smith; Yu-Chi Lee; Francisco Nicolás; Jose M Ordovás Journal: PLoS One Date: 2011-02-28 Impact factor: 3.240
Authors: L J Kopplin; R P Igo; Y Wang; T A Sivakumaran; S A Hagstrom; N S Peachey; P J Francis; M L Klein; J P SanGiovanni; E Y Chew; G J T Pauer; G M Sturgill; T Joshi; L Tian; Q Xi; A K Henning; K E Lee; R Klein; B E K Klein; S K Iyengar Journal: Genes Immun Date: 2010-09-23 Impact factor: 2.676
Authors: Anna Schnell; Sylvie Chappuis; Isabelle Schmutz; Emanuele Brai; Jürgen A Ripperger; Olivier Schaad; Hans Welzl; Patrick Descombes; Lavinia Alberi; Urs Albrecht Journal: PLoS One Date: 2014-06-16 Impact factor: 3.240
Authors: Heather S L Jim; Hui-Yi Lin; Jonathan P Tyrer; Kate Lawrenson; Joe Dennis; Ganna Chornokur; Zhihua Chen; Ann Y Chen; Jennifer Permuth-Wey; Katja Kh Aben; Hoda Anton-Culver; Natalia Antonenkova; Fiona Bruinsma; Elisa V Bandera; Yukie T Bean; Matthias W Beckmann; Maria Bisogna; Line Bjorge; Natalia Bogdanova; Louise A Brinton; Angela Brooks-Wilson; Clareann H Bunker; Ralf Butzow; Ian G Campbell; Karen Carty; Jenny Chang-Claude; Linda S Cook; Daniel W Cramer; Julie M Cunningham; Cezary Cybulski; Agnieszka Dansonka-Mieszkowska; Andreas du Bois; Evelyn Despierre; Weiva Sieh; Jennifer A Doherty; Thilo Dörk; Matthias Dürst; Douglas F Easton; Diana M Eccles; Robert P Edwards; Arif B Ekici; Peter A Fasching; Brooke L Fridley; Yu-Tang Gao; Aleksandra Gentry-Maharaj; Graham G Giles; Rosalind Glasspool; Marc T Goodman; Jacek Gronwald; Philipp Harter; Hanis N Hasmad; Alexander Hein; Florian Heitz; Michelle A T Hildebrandt; Peter Hillemanns; Claus K Hogdall; Estrid Hogdall; Satoyo Hosono; Edwin S Iversen; Anna Jakubowska; Allan Jensen; Bu-Tian Ji; Beth Y Karlan; Melissa Kellar; Lambertus A Kiemeney; Camilla Krakstad; Susanne K Kjaer; Jolanta Kupryjanczyk; Robert A Vierkant; Diether Lambrechts; Sandrina Lambrechts; Nhu D Le; Alice W Lee; Shashi Lele; Arto Leminen; Jenny Lester; Douglas A Levine; Dong Liang; Boon Kiong Lim; Jolanta Lissowska; Karen Lu; Jan Lubinski; Lene Lundvall; Leon F A G Massuger; Keitaro Matsuo; Valerie McGuire; John R McLaughlin; Ian McNeish; Usha Menon; Roger L Milne; Francesmary Modugno; Lotte Thomsen; Kirsten B Moysich; Roberta B Ness; Heli Nevanlinna; Ursula Eilber; Kunle Odunsi; Sara H Olson; Irene Orlow; Sandra Orsulic; Rachel Palmieri Weber; James Paul; Celeste L Pearce; Tanja Pejovic; Liisa M Pelttari; Malcolm C Pike; Elizabeth M Poole; Eva Schernhammer; Harvey A Risch; Barry Rosen; Mary Anne Rossing; Joseph H Rothstein; Anja Rudolph; Ingo B Runnebaum; Iwona K Rzepecka; Helga B Salvesen; Ira Schwaab; Xiao-Ou Shu; Yurii B Shvetsov; Nadeem Siddiqui; Honglin Song; Melissa C Southey; Beata Spiewankiewicz; Lara Sucheston-Campbell; Soo-Hwang Teo; Kathryn L Terry; Pamela J Thompson; Ingvild L Tangen; Shelley S Tworoger; Anne M van Altena; Ignace Vergote; Christine S Walsh; Shan Wang-Gohrke; Nicolas Wentzensen; Alice S Whittemore; Kristine G Wicklund; Lynne R Wilkens; Anna H Wu; Xifeng Wu; Yin-Ling Woo; Hannah Yang; Wei Zheng; Argyrios Ziogas; Ernest Amankwah; Andrew Berchuck; Joellen M Schildkraut; Linda E Kelemen; Susan J Ramus; Alvaro N A Monteiro; Ellen L Goode; Steven A Narod; Simon A Gayther; Paul D P Pharoah; Thomas A Sellers; Catherine M Phelan Journal: J Genet Genome Res Date: 2015-09-15