Novel genetic variants in HDAC2 and PPARGC1A of the CREB-binding protein pathway predict survival of non-small-cell lung cancer.
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
Journal articleSubject
CREB-binding protein pathwaygenetic susceptibility
non-small-cell lung cancer
single-nucleotide polymorphisms
Permalink
https://hdl.handle.net/10161/19553Published Version (Please cite this version)
10.1002/mc.23132Publication Info
Tang, Dongfang; Zhao, Yu Chen; Qian, Danwen; Liu, Hongliang; Luo, Sheng; Patz, Edward
F; ... Wei, Qingyi (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
More Info
Show full item recordScholars@Duke
Carolyn Glass
Associate Professor of Pathology
Cardiac and Thoracic PathologistDivision Chief, Cardiovascular Pathology Co-Director,
Division of Artificial Intelligence and Computational PathologyDirector, Duke University
Hospital Autopsy Service Associate Residency Program Director
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&rsq
Sheng Luo
Professor of Biostatistics & Bioinformatics
Patricia Gripka Moorman
Professor Emeritus in Family Medicine and Community Health
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.
Edward F. Patz Jr.
James and Alice Chen Distinguished Professor of Radiology
There are numerous ongoing clinical studies primarily focused on the early detection
of cancer.
The basic science investigations in our laboratory concentration on three fundamental
translational areas, 1) Development of molecular imaging probes - We have used several
different approaches to develop novel imaging probes that characterize and phenotype
tumors. 2) Discovery of novel lung cancer biomarkers - We ex
Alphabetical list of authors with Scholars@Duke profiles.

Articles written by Duke faculty are made available through the campus open access policy. For more information see: Duke Open Access Policy
Rights for Collection: Scholarly Articles
Works are deposited here by their authors, and represent their research and opinions, not that of Duke University. Some materials and descriptions may include offensive content. More info