Novel genetic variants in HDAC2 and PPARGC1A of the CREB-binding protein pathway predict survival of non-small-cell lung cancer.
Date
2019-11-12
Journal Title
Journal ISSN
Volume Title
Repository Usage Stats
views
downloads
Citation Stats
Abstract
The CREB-binding protein (CBP) pathway plays an important role in transcription and activity of acetyltransferase that acetylates lysine residues of histones and nonhistone proteins. In the present study, we hypothesized that genetic variants in the CBP pathway genes played a role in survival of non-small-cell lung cancer (NSCLC). We tested this hypothesis using the genotyping data from the genome-wide association study (GWAS) dataset from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. In the single-locus analysis, we evaluated associations between 13 176 (1107 genotyped and 12 069 imputed) single-nucleotide polymorphisms (SNPs) in 72 genes and survival of 1185 patients with NSCLC. The identified 106 significant SNPs in the discovery were further validated in additional genotyping data from another GWAS dataset of 984 patients with NSCLC in the Harvard Lung Cancer Susceptibility Study. The combined results of two datasets showed that two independent, potentially functional SNPs (i.e., HDAC2 rs13213007G>A and PPARGC1A rs60571065T>A) were significantly associated with NSCLC overall survival, with a combined hazards ratio (HR) of 1.26 (95% confidence interval (CI), 1.09-1.45; P = .002) and 1.23 (1.04-1.47; P = .017), respectively. Furthermore, we performed an expression quantitative trait loci analysis and found that the survival-associated HDAC2 rs13213007A allele (GA+AA), but not PPARGC1A rs60571065A allele (TA+AA), was significantly associated with increased messenger RNA expression levels of HDAC2 in 373 lymphoblastoid cell lines. These results indicate that the HDAC2 rs13213007A allele is a potential predictor of NSCLC survival, likely by altering the HDAC2 expression.
Type
Department
Description
Provenance
Citation
Permalink
Published Version (Please cite this version)
Publication Info
Tang, Dongfang, Yu Chen Zhao, Danwen Qian, Hongliang Liu, Sheng Luo, Edward F Patz, Patricia G Moorman, Li Su, et al. (2019). Novel genetic variants in HDAC2 and PPARGC1A of the CREB-binding protein pathway predict survival of non-small-cell lung cancer. Molecular carcinogenesis. 10.1002/mc.23132 Retrieved from https://hdl.handle.net/10161/19553.
This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
Collections
Scholars@Duke

Sheng Luo

Patricia Gripka Moorman
Dr. Moorman's research focuses on the epidemiology of women's health issues. Her work includes research on ovarian cancer, breast cancer and hysterectomy. Areas of particular interest include disparities in cancer risk factors and outcomes and the effects of hysterectomy on ovarian function. As part of the Duke Evidence Synthesis group, she has also been involved in systematic reviews and meta-analyses related to ovarian cancer, breast cancer and infertility.

Carolyn Glass
Cardiothoracic Pathologist and Physician-Scientist
Division Chief, Cardiovascular Pathology
Co-Director, Division of Artificial Intelligence and Computational Pathology
Associate Director, Residency Program
Director, Duke University Hospital Autopsy Service
Dr. Glass completed medical residency in Anatomic Pathology at the Brigham and Women’s Hospital/Harvard Medical School followed by fellowships in Cardiothoracic Pathology also at Brigham and Women’s Hospital/Harvard Medical School and Pulmonary/Cardiac Transplant Pathology at the University of Texas Southwestern Medical Center. Dr. Glass initially trained as a vascular surgeon with a focus on endovascular/interventional procedures through the 0+5 Integrated Vascular Surgery Program at the University of Rochester Medical Center from 2007-2011. As a recipient of the NIH National Lung Blood Institute T32 Ruth Kirschstein National Service Research Award, she completed a Ph.D with a concentration in Genomics and Epigenetics in 2014. Dr. Glass serves as P.I. of multiple NIH grants, including U54 and SBIR.
As a thoracic surgical pathologist, Dr. Glass diagnoses complex heart transplant rejection and thoracic malignancies. She works closely with the Duke Thoracic Oncology Group, DCI Center for Cancer Immunotherapy, Duke Division of Cardiovascular Medicine and Cardiothoracic Surgery and Pratt School of Biomedical Engineering.
Dr. Glass is the recipient of the Society of Cardiovascular Pathology (SCVP) Young Investigator’s Award, the William von Liebig Vascular Biology Research Fellowship at the Harvard Institutes of Medicine, the Duke Pathology Salvatore V. Pizzo Faculty Research Mentor Award, the Duke Department of Pathology Early Career Research Achievement Award and is author of over 85 publications (including book chapters in the recent W.H.O. Classification Tumours of the Lung, Pleura, Thymus and Heart) and 50 national presentations in cardiovascular disease, thoracic malignancies, surgery and machine learning.
In addition to her clinical and research activities, Dr. Glass serves on the Executive/National Committees for the Society of Cardiovascular Pathology, College of American Pathology Artificial Intelligence Committee and the Duke School of Medicine Executive Admissions Committee.
Unless otherwise indicated, scholarly articles published by Duke faculty members are made available here with a CC-BY-NC (Creative Commons Attribution Non-Commercial) license, as enabled by the Duke Open Access Policy. If you wish to use the materials in ways not already permitted under CC-BY-NC, please consult the copyright owner. Other materials are made available here through the author’s grant of a non-exclusive license to make their work openly accessible.