Novel genetic variants in HDAC2 and PPARGC1A of the CREB-binding protein pathway predict survival of non-small-cell lung cancer.
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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.
SubjectCREB-binding protein pathway
non-small-cell lung cancer
Published Version (Please cite this version)10.1002/mc.23132
Publication InfoLuo, Sheng; Patz, Edward; Moorman, Patricia; Glass, Carolyn; Tang, Dongfang; Zhao, Yu Chen; ... 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.
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Assistant Professor of Pathology
Professor of Biostatistics & Bioinformatics
Professor 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.
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
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