title: Polymorphisms of the centrosomal gene (FGFR1OP) and lung cancer risk: a meta-analysis of 14,463 cases and 44,188 controls.
abstract: Centrosome abnormalities are often observed in premalignant lesions and in situ tumors and have been associated with aneuploidy and tumor development. We investigated the associations of 9354 single-nucleotide polymorphisms (SNPs) in 106 centrosomal genes with lung cancer risk by first using the summary data from six published genome-wide association studies (GWASs) of the Transdisciplinary Research in Cancer of the Lung (TRICL) (12,160 cases and 16 838 controls) and then conducted in silico replication in two additional independent lung cancer GWASs of Harvard University (984 cases and 970 controls) and deCODE (1319 cases and 26,380 controls). A total of 44 significant SNPs with false discovery rate (FDR) ≤ 0.05 were mapped to one novel gene FGFR1OP and two previously reported genes (TUBB and BRCA2). After combined the results from TRICL with those from Harvard and deCODE, the most significant association (P combined = 8.032 × 10(-6)) was with rs151606 within FGFR1OP. The rs151606 T>G was associated with an increased risk of lung cancer [odds ratio (OR) = 1.10, 95% confidence interval (95% CI) = 1.05-1.14]. Another significant tagSNP rs12212247 T>C (P combined = 9.589 × 10(-6)) was associated with a decreased risk of lung cancer (OR = 0.93, 95% CI = 0.90-0.96). Further in silico functional analyzes revealed that rs151606 might affect transcriptional regulation and result in decreased FGFR1OP expression (P trend = 0.022). The findings shed some new light on the role of centrosome abnormalities in the susceptibility to lung carcinogenesis.
authors.affiliation: Duke Cancer Institute and.|Division of Cardiovascular and Thoracic Surgery, Department of Surgery, Duke University Medical Center, 905 S. LaSalle Street, Durham, NC 27710, USA.|Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Surgery I, Peking University Cancer Hospital and Institute, Beijing 100142, China.
authors.forename: Xiaozheng
authors.initials: X
authors.lastname: Kang
authors.affiliation: Duke Cancer Institute and.|Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: Hongliang
authors.initials: H
authors.lastname: Liu
authors.affiliation: Duke Cancer Institute and.|Division of Cardiovascular and Thoracic Surgery, Department of Surgery, Duke University Medical Center, 905 S. LaSalle Street, Durham, NC 27710, USA.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Onaitis
authors.affiliation: Duke Cancer Institute and.|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 and.|Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Kouros
authors.initials: K
authors.lastname: Owzar
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: Massachusetts General Hospital, Boston, MA 02114, USA.|Department of Environmental Health, Harvard School of Public Health, Boston, MA 02115, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Su
authors.affiliation: Massachusetts General Hospital, Boston, MA 02114, USA.|Department of Environmental Health, Harvard School of Public Health, Boston, MA 02115, USA.
authors.forename: Yongyue
authors.initials: Y
authors.lastname: Wei
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: Bickeböller
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
authors.initials: N
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 Teresa
authors.initials: MT
authors.lastname: Landi
authors.affiliation: Helmholtz Centre Munich , German Research Centre for Environmental Health , Institute of Epidemiology I , 85764 Neuherberg , Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Heinrich
authors.affiliation: Department of Molecular Biology , University of Salzburg , 5020 Salzburg , Austria and.
authors.forename: Angela
authors.initials: A
authors.lastname: Risch
authors.affiliation: Department of Epidemiology , University of Texas MD Anderson Cancer Center , Houston , TX 77030 , USA.
authors.forename: Xifeng
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Epidemiology , University of Texas MD Anderson Cancer Center , Houston , TX 77030 , USA.
authors.forename: Yuanqing
authors.initials: Y
authors.lastname: Ye
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 and.|Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Wei
mesh_terms: D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D012307:Risk Factors
chemical_list: C117597:CEP43 protein, human; D011518:Proto-Oncogene Proteins