Large-scale whole exome sequencing studies identify two genes,CTSL and APOE, associated with lung cancer.

Humans Bayes Theorem Exome Sequencing Lung Neoplasms / genetics Case-Control Studies Apolipoproteins E / genetics

Journal

PLoS genetics
ISSN: 1553-7404
Titre abrégé: PLoS Genet
Pays: United States
ID NLM: 101239074

Informations de publication

Date de publication:
09 2023
Historique:
received: 23 12 2022
accepted: 07 08 2023
medline: 25 9 2023
pubmed: 22 9 2023
entrez: 22 9 2023
Statut: epublish

Résumé

Common genetic variants associated with lung cancer have been well studied in the past decade. However, only 12.3% heritability has been explained by these variants. In this study, we investigate the contribution of rare variants (RVs) (minor allele frequency <0.01) to lung cancer through two large whole exome sequencing case-control studies. We first performed gene-based association tests using a novel Bayes Factor statistic in the International Lung Cancer Consortium, the discovery study (European, 1042 cases vs. 881 controls). The top genes identified are further assessed in the UK Biobank (European, 630 cases vs. 172 864 controls), the replication study. After controlling for the false discovery rate, we found two genes, CTSL and APOE, significantly associated with lung cancer in both studies. Single variant tests in UK Biobank identified 4 RVs (3 missense variants) in CTSL and 2 RVs (1 missense variant) in APOE stongly associated with lung cancer (OR between 2.0 and 139.0). The role of these genetic variants in the regulation of CTSL or APOE expression remains unclear. If such a role is established, this could have important therapeutic implications for lung cancer patients.

Identifiants

DOI: 10.1371/journal.pgen.1010902 PMID: 37738239 PMC: PMC10516417
pubmed: 37738239
doi: 10.1371/journal.pgen.1010902
pii: PGENETICS-D-22-01475
pmc: PMC10516417
doi:

Substances chimiques

Apolipoproteins E 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e1010902

Subventions

Organisme : NCI NIH HHS
ID : U01 CA209414
Pays : United States
Organisme : NCI NIH HHS
ID : U19 CA203654
Pays : United States

Informations de copyright

Copyright: © 2023 Xu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Déclaration de conflit d'intérêts

The authors have declared that no competing interests exist.

Références

Nucleic Acids Res. 2003 Jul 1;31(13):3812-4
pubmed: 12824425
Pharmacol Ther. 2015 Nov;155:105-16
pubmed: 26299995
Biometrics. 2021 Mar;77(1):316-328
pubmed: 32277476
Hum Mol Genet. 2012 Nov 15;21(22):4980-95
pubmed: 22899653
Nat Genet. 2014 Mar;46(3):310-5
pubmed: 24487276
Nat Genet. 2021 Jul;53(7):942-948
pubmed: 34183854
Nat Genet. 2014 Jul;46(7):736-41
pubmed: 24880342
Am J Hum Genet. 2011 Jul 15;89(1):82-93
pubmed: 21737059
Curr Opin Oncol. 2009 Mar;21(2):99-104
pubmed: 19532009
Cancer Res. 2005 Jan 1;65(1):331-7
pubmed: 15665311
Am J Public Health. 1987 Apr;77(4):425-31
pubmed: 3826460
NPJ Precis Oncol. 2021 Feb 16;5(1):12
pubmed: 33594163
Tumour Biol. 2016 Aug;37(8):10715-21
pubmed: 26873483
Lung Cancer. 2011 Jan;71(1):28-33
pubmed: 20430468
Oncol Lett. 2011 Jul;2(4):693-699
pubmed: 22848251
Genome Biol. 2016 Jun 06;17(1):122
pubmed: 27268795
Lung Cancer. 2011 Apr;72(1):9-15
pubmed: 21272954
Biol Chem. 2010 Aug;391(8):913-22
pubmed: 20536383
Nat Genet. 2020 Sep;52(9):969-983
pubmed: 32839606
Nature. 2021 Nov;599(7886):628-634
pubmed: 34662886
J Thorac Oncol. 2018 Oct;13(10):1483-1495
pubmed: 29981437
Cancer Gene Ther. 2001 Jul;8(7):522-8
pubmed: 11498774
Cancer Cell Int. 2007 May 08;7:8
pubmed: 17488522
J Cancer Res Clin Oncol. 2022 Mar;148(3):599-608
pubmed: 34807310
Nat Genet. 2017 Jul;49(7):1126-1132
pubmed: 28604730
Nucleic Acids Res. 2019 Jan 8;47(D1):D886-D894
pubmed: 30371827
Cancer Res. 1991 Mar 1;51(5):1478-81
pubmed: 1997186
Cancer Gene Ther. 2003 Feb;10(2):141-51
pubmed: 12536203
Nature. 2018 Oct;562(7726):203-209
pubmed: 30305743
Signal Transduct Target Ther. 2021 Mar 27;6(1):134
pubmed: 33774649
Eur J Cancer. 2000 Apr;36(6):787-95
pubmed: 10762753
Nat Methods. 2010 Apr;7(4):248-9
pubmed: 20354512
Arch Med Res. 2008 Oct;39(7):663-7
pubmed: 18760194
Cell. 2012 Nov 21;151(5):1068-82
pubmed: 23142051
CA Cancer J Clin. 2018 Nov;68(6):394-424
pubmed: 30207593
Nature. 2009 Oct 8;461(7265):747-53
pubmed: 19812666

Auteurs

Jingxiong Xu (J)

Prosserman Centre for Population Health Research, Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, Ontario, Canada.
ORCID: 0000-0003-2193-2678

Wei Xu (W)

Princess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada.
Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.

Jiyeon Choi (J)

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America.

Yonathan Brhane (Y)

Prosserman Centre for Population Health Research, Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, Ontario, Canada.

David C Christiani (DC)

T. H. Chan School of Public Health, Harvard University, Boston, Massachusetts, United States of America.

Jui Kothari (J)

Department of Environmental Health, T. H. Chan School of Public Health, Harvard University, Boston, Massachusetts, United States of America.
ORCID: 0000-0002-8491-6256

James McKay (J)

International Agency for Research on Cancer, Lyon, France.

John K Field (JK)

Department of Molecular and Clinical Cancer Medicine, The University of Liverpool, Liverpool, United Kingdom.

Michael P A Davies (MPA)

Department of Molecular and Clinical Cancer Medicine, The University of Liverpool, Liverpool, United Kingdom.

Geoffrey Liu (G)

Princess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada.
Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.

Christopher I Amos (CI)

Dan L. Duncan Comprehensive Cancer Center, Department of Medicine, Baylor College of Medicine, Houston, Texas, United States of America.
Institute for Clinical and Translational Research, Baylor College of Medicine, Houston, Texas, United States of America.

Rayjean J Hung (RJ)

Prosserman Centre for Population Health Research, Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, Ontario, Canada.
Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
ORCID: 0000-0002-4486-7496

Laurent Briollais (L)

Prosserman Centre for Population Health Research, Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, Ontario, Canada.
Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
ORCID: 0000-0001-5741-9812

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