title: Genetic variants of PTPN2 are associated with lung cancer risk: a re-analysis of eight GWASs in the TRICL-ILCCO consortium.
abstract: The T-cell protein tyrosine phosphatase (TCPTP) pathway consists of signaling events mediated by TCPTP. Mutations and genetic variants of some genes in the TCPTP pathway are associated with lung cancer risk and survival. In the present study, we first investigated associations of 5,162 single nucleotide polymorphisms (SNPs) in 43 genes of this TCPTP pathway with lung cancer risk by using summary data of six published genome-wide association studies (GWAS) of 12,160 cases and 16,838 controls. We identified 11 independent SNPs in eight genes after correction for multiple comparisons by a false discovery rate <0.20. Then, we performed in silico functional analyses for these 11 SNPs by eQTL analysis, two of which, PTPN2 SNPs rs2847297 and rs2847282, were chosen as tagSNPs. We further included two additional GWAS datasets of Harvard University (984 cases and 970 controls) and deCODE (1,319 cases and 26,380 controls), and the overall effects of these two SNPs among all eight GWAS studies remained significant (OR = 0.95, 95% CI = 0.92-0.98, and P = 0.004 for rs2847297; OR = 0.95, 95% CI = 0.92-0.99, and P = 0.009 for rs2847282). In conclusion, the PTPN2 rs2847297 and rs2847282 may be potential susceptible loci for lung cancer risk.
authors.affiliation: Department of Respiration, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.|Duke Cancer Institute, Duke University Medical Center, Durham, NC, 27710, USA.|Department of Medicine, Duke University School of Medicine, Durham, NC, 27710, USA.
authors.forename: Yun
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Duke Cancer Institute, Duke University Medical Center, Durham, NC, 27710, USA.|Department of Medicine, Duke University School of Medicine, Durham, NC, 27710, USA.
authors.forename: Yanru
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Duke Cancer Institute, Duke University Medical Center, Durham, NC, 27710, USA.|Department of Medicine, Duke University School of Medicine, Durham, NC, 27710, USA.
authors.forename: Hongliang
authors.identifier: http://orcid.org/0000-0001-7639-0904
authors.initials: H
authors.lastname: Liu
authors.affiliation: Duke Cancer Institute, Duke University Medical Center, Durham, NC, 27710, USA.|Department of Medicine, Duke University School of Medicine, Durham, NC, 27710, USA.
authors.forename: Zhensheng
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Duke Cancer Institute, Duke University Medical Center, Durham, NC, 27710, USA.|Department of Medicine, Duke University School of Medicine, Durham, NC, 27710, USA.
authors.forename: Coleman
authors.initials: C
authors.lastname: Mills
authors.affiliation: Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Hanover, NH, 03755, USA.
authors.forename: Younghun
authors.initials: Y
authors.lastname: Han
authors.affiliation: Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: Rayjean J
authors.initials: RJ
authors.lastname: Hung
authors.affiliation: Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: Yonathan
authors.initials: Y
authors.lastname: Brhane
authors.affiliation: Public Health Ontario, Toronto, Ontario, M5T 3L9, Canada.
authors.forename: John
authors.initials: J
authors.lastname: McLaughlin
authors.affiliation: Genetic Epidemiology Group, International Agency for Research on Cancer (IARC), 69372, Lyon, France.
authors.forename: Paul
authors.initials: P
authors.lastname: Brennan
authors.affiliation: Department of Genetic Epidemiology, University Medical Center, Georg-August-University Göttingen, 37073, Göttingen, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Bickeboeller
authors.affiliation: Department of Genetic Epidemiology, University Medical Center, Georg-August-University Göttingen, 37073, Göttingen, Germany.
authors.forename: Albert
authors.initials: A
authors.lastname: Rosenberger
authors.affiliation: Division of Genetics and Epidemiology, the Institute of Cancer Research, London, SW7 3RP, UK.
authors.forename: Richard S
authors.initials: RS
authors.lastname: Houlston
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
authors.forename: Neil E
authors.initials: NE
authors.lastname: Caporaso
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Teresa Landi
authors.affiliation: Helmholtz Centre Munich, German Research Centre for Environmental Health, Institute of Epidemiology I, 85764, Neuherberg, Germany.
authors.forename: Irene
authors.initials: I
authors.lastname: Brueske
authors.affiliation: Department of Molecular Biology, University of Salzburg, 5020, Salzburg, Austria.
authors.forename: Angela
authors.initials: A
authors.lastname: Risch
authors.affiliation: Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
authors.forename: Yuanqing
authors.initials: Y
authors.lastname: Ye
authors.affiliation: Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
authors.forename: Xifeng
authors.initials: X
authors.lastname: Wu
authors.affiliation: Massachusetts General Hospital, Boston, MA 02114, USA, Department of Environmental Health, Harvard School of Public Health, Boston, MA, 02115, USA.
authors.forename: David C
authors.initials: DC
authors.lastname: Christiani
authors.affiliation: Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Hanover, NH, 03755, USA.
authors.forename: Christopher I
authors.initials: CI
authors.lastname: Amos
authors.affiliation: Duke Cancer Institute, Duke University Medical Center, Durham, NC, 27710, USA. qingyi.wei@duke.edu.|Department of Medicine, Duke University School of Medicine, Durham, NC, 27710, USA. qingyi.wei@duke.edu.
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Wei
mesh_terms: D055106:Genome-Wide Association Study; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D054578:Protein Tyrosine Phosphatase, Non-Receptor Type 2 / Q000235:genetics*
chemical_list: C516649:PTPN2 protein, human; D054578:Protein Tyrosine Phosphatase, Non-Receptor Type 2