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Genetic variants of PTPN2 are associated with lung cancer risk: a re-analysis of eight GWASs in the TRICL-ILCCO consortium.

About this Publication
Title
Genetic variants of PTPN2 are associated with lung cancer risk: a re-analysis of eight GWASs in the TRICL-ILCCO consortium.
Pubmed ID
28400551 (View this publication on the PubMed website)
Digital Object Identifier
Publication
Sci Rep. 2017 Apr 11; Volume 7 (Issue 1): Pages 825
Authors
Feng Y, Wang Y, Liu H, Liu Z, Mills C, Han Y, Hung RJ, Brhane Y, McLaughlin J, Brennan P, Bickeboeller H, Rosenberger A, Houlston RS, Caporaso NE, Teresa Landi M, Brueske I, Risch A, Ye Y, Wu X, Christiani DC, ...show more Amos CI, Wei Q
Affiliations
  • 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.
  • Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Hanover, NH, 03755, USA.
  • Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario, Canada.
  • Public Health Ontario, Toronto, Ontario, M5T 3L9, Canada.
  • Genetic Epidemiology Group, International Agency for Research on Cancer (IARC), 69372, Lyon, France.
  • Department of Genetic Epidemiology, University Medical Center, Georg-August-University Göttingen, 37073, Göttingen, Germany.
  • Division of Genetics and Epidemiology, the Institute of Cancer Research, London, SW7 3RP, UK.
  • Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
  • Helmholtz Centre Munich, German Research Centre for Environmental Health, Institute of Epidemiology I, 85764, Neuherberg, Germany.
...show more
  • Department of Molecular Biology, University of Salzburg, 5020, Salzburg, Austria.
  • Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
  • Massachusetts General Hospital, Boston, MA 02114, USA, Department of Environmental Health, Harvard School of Public Health, Boston, MA, 02115, USA.
  • Duke Cancer Institute, Duke University Medical Center, Durham, NC, 27710, USA. qingyi.wei@duke.edu.
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.

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