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Sökning: onr:"swepub:oai:lup.lub.lu.se:a3bb558f-a028-44a5-88aa-2154baba8cc5" > Systematic analyses...

Systematic analyses of regulatory variants in DNase I hypersensitive sites identified two novel lung cancer susceptibility loci

Dai, Juncheng, (författare)
Nanjing Medical University
Li, Zhihua, (författare)
First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University
Amos, Christopher I., (författare)
Dartmouth College
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Hung, Rayjean J., (författare)
University of Toronto, Sinai Health System
Tardon, Adonina, (författare)
CIBER Epidemiology and Public Health (CIBERESP), University of Oviedo
Andrew, Angeline S., (författare)
Norris Cotton Cancer Center
Chen, Chu, (författare)
Fred Hutchinson Cancer Research Center
Christiani, David C., (författare)
Harvard University
Albanes, Demetrios, (författare)
National Cancer Institute, USA
van der Heijden, Erik H.F.M., (författare)
Radboud University Medical Center
Duell, Eric J., (författare)
Catalan Institute of Oncology
Rennert, Gad, (författare)
Carmel Medical Center
Mckay, James D., (författare)
International Agency for Research on Cancer, World Health Organization
Yuan, Jian Min, (författare)
University of Pittsburgh Cancer Institute
Field, John K., (författare)
University of Liverpool
Manjer, Jonas, (författare)
Forskargrupper vid Lunds universitet, Lund University Research Groups, Lunds universitet, Lund University, Kirurgi, Surgery, Skåne University Hospital
Grankvist, Kjell, (författare)
Umeå University
Le Marchand, Loic, (författare)
University of Hawaii at Manoa
Teare, M. Dawn, (författare)
University of Sheffield
Schabath, Matthew B., (författare)
H. Lee Moffitt Cancer Center & Research Institute
Aldrich, Melinda C., (författare)
Vanderbilt University
Tsao, Ming Sound, (författare)
Princess Margaret Hospital University of Toronto
Lazarus, Philip, (författare)
Washington State University
Lam, Stephen, (författare)
British Columbia Cancer Agency
Bojesen, Stig E., (författare)
Gentofte Hospital, University of Copenhagen
Arnold, Susanne, (författare)
University of Kentucky Medical Center
Wu, Xifeng, (författare)
University of Texas
Haugen, Aage, (författare)
National Institute of Occupational Health, Norway
Janout, Vladimir, (författare)
Palacký University
Johansson, Mikael, (författare)
Umeå University
Brhane, Yonathan, (författare)
University of Toronto, Sinai Health System
Fernandez-Somoano, Ana, (författare)
CIBER Epidemiology and Public Health (CIBERESP), University of Oviedo
Kiemeney, Lambertus A., (författare)
Radboud University Medical Center
Davies, Michael P.A., (författare)
University of Liverpool
Zienolddiny, Shanbeh, (författare)
National Institute of Occupational Health, Norway
Hu, Zhibin, (författare)
Nanjing Medical University
Shen, Hongbing, (författare)
Nanjing Medical University
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2019
Engelska 9 s.
Ingår i: Carcinogenesis. - Oxford University Press. - 0143-3334. ; 40:3, s. 432-440
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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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.

Ämnesord

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 grundvetenskaper -- Medicinsk genetik (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Medical Genetics (hsv//eng)

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