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Systematic analyses of regulatory variants in DNase I hypersensitive sites identified two novel lung cancer susceptibility loci
J. Dai, Z. Li, CI. Amos, RJ. Hung, A. Tardon, AS. Andrew, C. Chen, DC. Christiani, D. Albanes, EHFM. van der Heijden, EJ. Duell, G. Rennert, JD. Mckay, JM. Yuan, JK. Field, J. Manjer, K. Grankvist, L. Le Marchand, MD. Teare, MB. Schabath, MC....
Jazyk angličtina Země Velká Británie
Typ dokumentu časopisecké články, práce podpořená grantem
Grantová podpora
R35 CA197449
NCI NIH HHS - United States
U01 CA167462
NCI NIH HHS - United States
K07 CA172294
NCI NIH HHS - United States
P50 CA119997
NCI NIH HHS - United States
P30 CA076292
NCI NIH HHS - United States
001
World Health Organization - International
U01 CA164973
NCI NIH HHS - United States
NLK
Free Medical Journals
od 1996 do Před 1 rokem
Open Access Digital Library
od 1996-01-01
Medline Complete (EBSCOhost)
od 1996-01-01 do Před 1 rokem
PubMed
30590402
DOI
10.1093/carcin/bgy187
Knihovny.cz E-zdroje
- MeSH
- deoxyribonukleasa I metabolismus MeSH
- genetická predispozice k nemoci * MeSH
- jednonukleotidový polymorfismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- lokus kvantitativního znaku MeSH
- nádory plic genetika MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
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.
Biomedical Data Science Geisel School of Medicine Dartmouth College Hanover NH USA
British Columbia Cancer Agency Vancouver British Columbia Canada
Clalit National Cancer Control Center Carmel Medical Center Haifa Israel
Department of Cancer Epidemiology H Lee Moffitt Cancer Center and Research Institute Tampa FL USA
Department of Epidemiology University of Texas MD Anderson Cancer Center Houston TX USA
Department of Medical Biosciences Umeå University Umeå Sweden
Department of Pharmaceutical Sciences College of Pharmacy Washington State University Spokane WA USA
Department of Radiation Sciences Umeå University Umeå Sweden
Division of Cancer Epidemiology and Genetics National Cancer Institute Bethesda MD USA
Division of Medical Oncology Markey Cancer Center Lexington KY USA
Epidemiology Program University of Hawai'i Cancer Center Honolulu HI USA
Faculty of Medicine IUOPA University of Oviedo and CIBERESP Oviedo Spain
International Agency for Research on Cancer World Health Organization Lyon France
Norris Cotton Cancer Center Geisel School of Medicine Hanover NH USA
Princess Margaret Cancer Centre Toronto Ontario Canada
Public Health Sciences Division Fred Hutchinson Cancer Research Center Seattle WA USA
Radboud University Medical Center Radboud Institute for Health Sciences Nijmegen The Netherlands
School of Health and Related Research University of Sheffield Sheffield South Yorkshire UK
Unit of Nutrition and Cancer Catalan Institute of Oncology Barcelona Spain
Citace poskytuje Crossref.org
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- $a Dai, Juncheng $u Department of Epidemiology, Center for Global Health, International Joint Research Center, School of Public Health, Nanjing Medical University, Nanjing, China. Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Jiangsu Collaborative Innovation Center of Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China.
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- $a Systematic analyses of regulatory variants in DNase I hypersensitive sites identified two novel lung cancer susceptibility loci / $c J. Dai, Z. Li, CI. Amos, RJ. Hung, A. Tardon, AS. Andrew, C. Chen, DC. Christiani, D. Albanes, EHFM. van der Heijden, EJ. Duell, G. Rennert, JD. Mckay, JM. Yuan, JK. Field, J. Manjer, K. Grankvist, L. Le Marchand, MD. Teare, MB. Schabath, MC. Aldrich, MS. Tsao, P. Lazarus, S. Lam, SE. Bojesen, S. Arnold, X. Wu, A. Haugen, V. Janout, M. Johansson, Y. Brhane, A. Fernandez-Somoano, LA. Kiemeney, MPA. Davies, S. Zienolddiny, Z. Hu, H. Shen,
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