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Systematic analyses...
Systematic analyses of regulatory variants in DNase I hypersensitive sites identified two novel lung cancer susceptibility loci
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- Dai, Juncheng (author)
- Nanjing Medical University
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- Li, Zhihua (author)
- First Affiliated Hospital of Nanjing Medical University
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- Amos, Christopher I. (author)
- Dartmouth College
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- Hung, Rayjean J. (author)
- Sinai Health System,University of Toronto
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- Tardon, Adonina (author)
- CIBER Epidemiology and Public Health (CIBERESP),University of Oviedo
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- Andrew, Angeline S. (author)
- Norris Cotton Cancer Center
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- Chen, Chu (author)
- Fred Hutchinson Cancer Research Center,Harvard University,Vanderbilt University
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- Christiani, David C. (author)
- Harvard University
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- Albanes, Demetrios (author)
- National Cancer Institute, USA
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- van der Heijden, Erik H.F.M. (author)
- Radboud University Medical Center
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- Duell, Eric J. (author)
- Catalan Institute of Oncology
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- Rennert, Gad (author)
- Carmel Medical Center
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- Mckay, James D. (author)
- International Agency for Research on Cancer, World Health Organization
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- Yuan, Jian Min (author)
- University of Pittsburgh Cancer Institute
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- Field, John K. (author)
- University of Liverpool
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- Manjer, Jonas (author)
- Lund University,Lunds universitet,Kirurgi,Forskargrupper vid Lunds universitet,Surgery,Lund University Research Groups,Skåne University Hospital
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- Grankvist, Kjell (author)
- Umeå universitet,Umeå University,Klinisk kemi
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- Le Marchand, Loic (author)
- University of Hawaii at Manoa
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- Teare, M. Dawn (author)
- University of Sheffield
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- Schabath, Matthew B. (author)
- H. Lee Moffitt Cancer Center & Research Institute
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- Aldrich, Melinda C. (author)
- Vanderbilt University
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- Tsao, Ming Sound (author)
- Princess Margaret Hospital University of Toronto
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- Lazarus, Philip (author)
- Washington State University
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- Lam, Stephen (author)
- British Columbia Cancer Agency
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- Bojesen, Stig E. (author)
- University of Copenhagen,Gentofte Hospital
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- Arnold, Susanne (author)
- University of Kentucky Medical Center
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- Wu, Xifeng (author)
- University of Texas
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- Haugen, Aage (author)
- National Institute of Occupational Health, Norway
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- Janout, Vladimir (author)
- Palacký University
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- Johansson, Mikael (author)
- Umeå universitet,Umeå University,Onkologi
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- Brhane, Yonathan (author)
- Sinai Health System,University of Toronto
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- Fernandez-Somoano, Ana (author)
- CIBER Epidemiology and Public Health (CIBERESP),University of Oviedo
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- Kiemeney, Lambertus A. (author)
- Radboud University Medical Center
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- Davies, Michael P.A. (author)
- University of Liverpool
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- Zienolddiny, Shanbeh (author)
- National Institute of Occupational Health, Norway
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- Hu, Zhibin (author)
- Nanjing Medical University
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- Shen, Hongbing (author)
- Nanjing Medical University
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(creator_code:org_t)
- 2019-01-09
- 2019
- English 9 s.
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In: Carcinogenesis. - : Oxford University Press (OUP). - 0143-3334 .- 1460-2180. ; 40:3, s. 432-440
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Dai, Juncheng
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Li, Zhihua
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Amos, Christophe ...
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Hung, Rayjean J.
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Tardon, Adonina
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Andrew, Angeline ...
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show more...
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Chen, Chu
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Christiani, Davi ...
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Albanes, Demetri ...
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van der Heijden, ...
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Duell, Eric J.
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Rennert, Gad
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Mckay, James D.
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Yuan, Jian Min
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Field, John K.
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Manjer, Jonas
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Grankvist, Kjell
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Le Marchand, Loi ...
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Teare, M. Dawn
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Schabath, Matthe ...
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Aldrich, Melinda ...
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Tsao, Ming Sound
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Lazarus, Philip
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Lam, Stephen
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Bojesen, Stig E.
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Arnold, Susanne
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Wu, Xifeng
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Haugen, Aage
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Janout, Vladimir
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Johansson, Mikae ...
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Brhane, Yonathan
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Fernandez-Somoan ...
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Kiemeney, Lamber ...
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Davies, Michael ...
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Zienolddiny, Sha ...
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Hu, Zhibin
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Shen, Hongbing
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Medical Genetics
- Articles in the publication
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Carcinogenesis
- By the university
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Lund University
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Umeå University