Renke Zhou1, Jeffrey S Wefel2, Erik P Sulman3, Nicholas S Boehling3, Georgina N Armstrong1, Spiridon Tsavachidis1, Fu-Wen Liang4, Carol J Etzel5, Lisa S Kahalley6, Brent J Small7, Michael E Scheurer1, Melissa L Bondy8, Yanhong Liu9. 1. Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, One Baylor Plaza, Mailstop BCM305, Houston, TX, 77030, USA. 2. Section of Neuropsychology, Department of Neuro-Oncology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 431, Houston, TX, 77030, USA. jwefel@mdanderson.org. 3. Department of Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, 77030, USA. 4. Institute of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan. 5. Biostatistics, Corrona, LLC, Southborough, MA, 01772, USA. 6. Department of Pediatrics, Baylor College of Medicine, Houston, TX, 77030, USA. 7. School of Aging Studies, University of South Florida, 4202 E Fowler Avenue, Tampa, FL, 33620, USA. 8. Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, One Baylor Plaza, Mailstop BCM305, Houston, TX, 77030, USA. mbondy@bcm.edu. 9. Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, One Baylor Plaza, Mailstop BCM305, Houston, TX, 77030, USA. yl10@bcm.edu.
Abstract
PURPOSE: Impaired neurocognitive function (NCF) is extremely common in patients with higher grade primary brain tumor. We previously reported evidence of genetic variants associated with NCF in glioma patients prior to treatment. However, little is known about the effect of genetic variants on NCF decline after adjuvant therapy. METHODS: Patients (N = 102) completed longitudinal NCF assessments that included measures of verbal memory, processing speed, and executive function. Testing was conducted in the postoperative period with an average follow up interval of 1.3 years. We examined polymorphisms in 580 genes related to five pathways (inflammation, DNA repair, metabolism, cognitive, and telomerase). RESULTS: Five polymorphisms were associated with longitudinal changes in processing speed and 14 polymorphisms with executive function. Change in processing speed was strongly associated with MCPH1 rs17631450 (P = 2.2 × 10-7) and CCDC26 rs7005206 (P = 9.3 × 10-7) in the telomerase pathway; while change in executive function was more strongly associated with FANCF rs1514084 (P = 2.9 × 10-6) in the DNA repair pathway and DAOA rs12428572 (P = 2.4 × 10-5) in the cognitive pathway. Joint effect analysis found significant genetic-dosage effects for longitudinal changes in processing speed (Ptrend = 1.5 × 10-10) and executive function (Ptrend = 2.1 × 10-11). In multivariable analyses, predictors of NCF decline included progressive disease, lower baseline NCF performance, and more at-risk genetic variants, after adjusting for age, sex, education, tumor location, histology, and disease progression. CONCLUSION: Our longitudinal analyses revealed that polymorphisms in telomerase, DNA repair, and cognitive pathways are independent predictors of decline in NCF in glioma patients.
PURPOSE: Impaired neurocognitive function (NCF) is extremely common in patients with higher grade primary brain tumor. We previously reported evidence of genetic variants associated with NCF in glioma patients prior to treatment. However, little is known about the effect of genetic variants on NCF decline after adjuvant therapy. METHODS: Patients (N = 102) completed longitudinal NCF assessments that included measures of verbal memory, processing speed, and executive function. Testing was conducted in the postoperative period with an average follow up interval of 1.3 years. We examined polymorphisms in 580 genes related to five pathways (inflammation, DNA repair, metabolism, cognitive, and telomerase). RESULTS: Five polymorphisms were associated with longitudinal changes in processing speed and 14 polymorphisms with executive function. Change in processing speed was strongly associated with MCPH1 rs17631450 (P = 2.2 × 10-7) and CCDC26 rs7005206 (P = 9.3 × 10-7) in the telomerase pathway; while change in executive function was more strongly associated with FANCF rs1514084 (P = 2.9 × 10-6) in the DNA repair pathway and DAOA rs12428572 (P = 2.4 × 10-5) in the cognitive pathway. Joint effect analysis found significant genetic-dosage effects for longitudinal changes in processing speed (Ptrend = 1.5 × 10-10) and executive function (Ptrend = 2.1 × 10-11). In multivariable analyses, predictors of NCF decline included progressive disease, lower baseline NCF performance, and more at-risk genetic variants, after adjusting for age, sex, education, tumor location, histology, and disease progression. CONCLUSION: Our longitudinal analyses revealed that polymorphisms in telomerase, DNA repair, and cognitive pathways are independent predictors of decline in NCF in glioma patients.
Authors: Denise D Correa; Lisa M DeAngelis; Weiji Shi; Howard T Thaler; Michael Lin; Lauren E Abrey Journal: J Neurooncol Date: 2006-07-19 Impact factor: 4.130
Authors: Yanhong Liu; Renke Zhou; Erik P Sulman; Michael E Scheurer; Nicholas Boehling; Georgina N Armstrong; Spiridon Tsavachidis; Fu-Wen Liang; Carol J Etzel; Charles A Conrad; Mark R Gilbert; Terri S Armstrong; Melissa L Bondy; Jeffrey S Wefel Journal: Clin Cancer Res Date: 2015-04-22 Impact factor: 12.531
Authors: Derek R Johnson; Allison M Sawyer; Christina A Meyers; Brian Patrick O'Neill; Jeffrey S Wefel Journal: Neuro Oncol Date: 2012-04-16 Impact factor: 12.300
Authors: M F Egan; T E Goldberg; B S Kolachana; J H Callicott; C M Mazzanti; R E Straub; D Goldman; D R Weinberger Journal: Proc Natl Acad Sci U S A Date: 2001-05-29 Impact factor: 11.205
Authors: Michael F Egan; Masami Kojima; Joseph H Callicott; Terry E Goldberg; Bhaskar S Kolachana; Alessandro Bertolino; Eugene Zaitsev; Bert Gold; David Goldman; Michael Dean; Bai Lu; Daniel R Weinberger Journal: Cell Date: 2003-01-24 Impact factor: 41.582
Authors: Terri S Armstrong; Jeffrey S Wefel; Meihua Wang; Mark R Gilbert; Minhee Won; Andrew Bottomley; Tito R Mendoza; Corneel Coens; Maria Werner-Wasik; David G Brachman; Ali K Choucair; Minesh Mehta Journal: J Clin Oncol Date: 2013-10-07 Impact factor: 44.544
Authors: David D Ward; Mathew J Summers; Nichole L Saunders; Pierce Janssen; Kimberley E Stuart; James C Vickers Journal: Behav Brain Res Date: 2014-06-16 Impact factor: 3.332