• Duke Cancer Institute and.
• Community and Family Medicine , Geisel School of Medicine , Dartmouth College , Hanover , NH 03755 , USA.
• Massachusetts General Hospital, Boston, MA 02114, 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.

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.