Abstract
DNase I hypersensitive sites (DHS) are abundant in regulatory elements, such as promoter, enhancer and transcription factor binding sites. Many studies have revealed that disease-associated variants were concentrated in DHS-related regions. However, limited studies are available on the roles of DHS-related variants in lung cancer. In this study, we performed a large-scale case-control study with 20 871 lung cancer cases and 15 971 controls to evaluate the associations between regulatory genetic variants in DHS and lung cancer susceptibility. The expression quantitative trait loci (eQTL) analysis and pathway-enrichment analysis were performed to identify the possible target genes and pathways. In addition, we performed motif-based analysis to explore the lung-cancer-related motifs using sequence kernel association test. Two novel variants, rs186332 in 20q13.3 (C>T, odds ratio [OR] = 1.17, 95% confidence interval [95% CI]: 1.10-1.24, P = 8.45 × 10-7) and rs4839323 in 1p13.2 (T>C, OR = 0.92, 95% CI: 0.89-0.95, P = 1.02 × 10-6) showed significant association with lung cancer risk. The eQTL analysis suggested that these two SNPs might regulate the expression of MRGBP and SLC16A1, respectively. What's more, the expression of both MRGBP and SLC16A1 was aberrantly elevated in lung tumor tissues. The motif-based analysis identified 10 motifs related to the risk of lung cancer (P < 1.71 × 10-4). Our findings suggested that variants in DHS might modify lung cancer susceptibility through regulating the expression of surrounding genes. This study provided us a deeper insight into the roles of DHS-related genetic variants for lung cancer.
Original language | English |
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Article number | bgy187 |
Pages (from-to) | 432-440 |
Number of pages | 9 |
Journal | Carcinogenesis |
Volume | 40 |
Issue number | 3 |
DOIs | |
State | Published - May 14 2019 |
Bibliographical note
Publisher Copyright:© 2019 The Author(s). Published by Oxford University Press. All rights reserved.
Funding
The Key international (regional) cooperative research project (81820108028); National Natural Science of China (81521004); the Priority Academic Program for the Development of Jiangsu Higher Education Institutions (Public Health and Preventive Medicine); Top-notch Academic Programs Project of Jiangsu Higher Education Institutions (PPZY2015A067).
Funders | Funder number |
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Top-notch Academic Programs Project of Jiangsu Higher Education Institutions | PPZY2015A067 |
National Childhood Cancer Registry – National Cancer Institute | P50CA119997 |
National Childhood Cancer Registry – National Cancer Institute | |
National Natural Science Foundation of China (NSFC) | 81521004 |
National Natural Science Foundation of China (NSFC) | |
Priority Academic Program Development of Jiangsu Higher Education Institutions |
ASJC Scopus subject areas
- Cancer Research