Associations between genetic variants in mRNA splicing-related genes and risk of lung cancer: a pathway-based analysis from published GWASs
Year: 2017
Type: article
Abstract: mRNA splicing is an important mechanism to regulate mRNA expression. Abnormal regulation of this process may lead to lung cancer. Here, we investigated the associations of 11,966 single-nucleotide polymorphisms (SNPs) in 206 mRNA splicing-related genes with lung cancer risk by using the summary data from six published genome-wide association studies (GWASs) of Transdisciplinary Research in Cancer of the Lung (TRICL) (12,160 cases and 16,838 controls) and another two lung cancer GWASs of Harvard University (984 cases and 970 controls) and deCODE (1,319 cases and 26,380 controls). We found that a total of 12 significant SNPs with false discovery rate (FDR) ≤0.05 were mapped to one novel gene PRPF6 and two previously reported genes (DHX16 and LSM2) that were also confirmed in this study. The six novel SNPs in PRPF6 were in high linkage disequilibrium and associated with PRPF6 mRNA expression in lymphoblastoid cells from 373 Europeans in the 1000 Genomes Project. Taken together, our studies shed new light on the role of mRNA splicing genes in the development of lung cancer.
Source: Scientific Reports
DOI: 10.1038/srep44634
Authors: Yongchu Pan, Hongliang Liu, Yanru Wang, Xiaozheng Kang, Zhensheng Liu, Kouros Owzar, Younghun Han, Li Su, Yongyue Wei, Rayjean J. Hung, Yonathan Brhane, John McLaughlin, Paul Brennan, Heike Bickeböller, Albert Rosenberger, Richard S. Houlston, Neil Caporaso, Maria Teresa Landi, Joachim Heinrich, Angela Risch, Xifeng Wu, Yuanqing Ye, David C. Christiani, Christopher I. Amos, Qingyi Wei
Institutions: Duke University, Duke Medical Center, Duke Cancer Institute, Nanjing Medical University, Dartmouth College, Harvard University, Massachusetts General Hospital, Mount Sinai Hospital, Lunenfeld-Tanenbaum Research Institute, Public Health Ontario, Centre international de recherche sur le cancer, Universitätsmedizin Göttingen, University of Göttingen, Institute of Cancer Research, National Institutes of Health, Division of Cancer Epidemiology and Genetics, Helmholtz Munich, University of Salzburg, The University of Texas MD Anderson Cancer Center
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,690
Funders: American Cancer Society, Sanofi, World Health Organization, Cancer Prevention and Research Institute of Texas, University of Minnesota, Henry Ford Health System, Johns Hopkins University, University of Pittsburgh, Georgetown University, Cancer Care Ontario, Roy Castle Lung Cancer Foundation, Wellcome Trust, Cancer Research UK, European Commission, Deutscher Akademischer Austauschdienst, Deutsche Forschungsgemeinschaft, Norges Forskningsråd, Deutsche Krebshilfe, Bundesamt für Strahlenschutz, Nanjing Medical University, Tartu Ülikool, National Institutes of Health, University of California, Los Angeles, University of Texas MD Anderson Cancer Center, University of Colorado Denver, Canadian Cancer Society Research Institute, European Regional Development Fund, National Institute on Drug Abuse, National Human Genome Research Institute, National Cancer Institute, Duke Cancer Institute, FP7 Research Potential of Convergence Regions
Awards: PROSTATE, LUNG, COLORECTAL &OVARIAN (PLCO) CANCER, Inflammation Genes and Lung Cancer Risk, PROSTATE, LUNG, COLORECTAL AND OVARIAN CANCER, PROSTATE, LUNG, COLORECTAL AND OVARIAN (PLCO) CANCER, Opening Estonian Genome Project for European Research Area, G1267016694, G1342751976, G1394878971, PROSTATE, LUNG, COLORECTAL, AND OVARIAN (PLCO) CANCER, G180930151, PROSTATE, LUNG, COLORECTAL AND OVARIAN (PLCO) CANCER, G2081079141, G2146332128, G216524704, PROSTATE, LUNG, COLORECTAL AND OVARIAN (PLCO) CANCER, PROSTATE, LUNG, COLORECTAL AND OVARIAN (PLCO) CANCER, Molecular and Genetic Analysis of Lung Cancer Survival, G2407800586, GENETICS OF TOBACCO AND ALCOHOL RELATED CANCERS, G2468562894, G2545803302, G265864768, G2787837681, FOLLOW-UP OF THE ALPHA-TOCOPHEROL, BETA-CAROTENE CANCER PREVENTION (ATBC) STUDY , PROSTATE, LUNG, COLORECTAL AND OVARIAN (PLCO) CANCER, PROSTATE, LUNG, COLORECTAL, &OVARIAN CANCER SCREENING, PROSTATE, LUNG, COLORECTAL &OVARIAN CANCER, PROSTATE, LUNG, COLORECTAL AND OVARIAN CANCER, G3143007284, G3166288362, Statistical Methods for Gene Environment Interactions In Lung Cancer, G3351748408, G3371416537, G3446191057, U S-FINLAND STUDIES OF NUTRITION AND CANCER, G3588481721, G3589027119, G3605022155, G3986927127, G4076209013, PROSTATE, LUNG, COLORECTAL AND OVARIAN (PLCO) CANCER, G4503763930, Genome Wide Association Coordinating Center, G4619280610, Dana-Farber/Harvard Cancer Center SPORE in Lung Cancer, Transdisciplinary Research in Cancer of the Lung (TRICL), Adenocarcinoma of the Lung: role of NNK susceptibility, G5043441381, Genes contributing for nicotine dependence in humans, G5198629111, G5241316884, G5324144389, G5544106795, G5574484903, G5715905319, G5734460833, Targeting Lung Cancer Vulnerabilities, SPORE in Lung Cancer, G5780585700, JH/CIDR Genotyping for Genome-Wide Association Studies, G6124801312, G6219625355, G6272369800, G6375054419, G650037044, MOLECULAR EPIDEMIOLOGY OF LUNG CANCER, High Density Association Analysis of Lung Cancer, G6916216771, Genetic Susceptibility to Lung Cancer, G7093047072, G7238814555, THE CAROTENE AND RETINOL EFFICACY TRIAL (CARET), G7400349024, G7421337856, G7442572985, G7762133158, G8020593023, Susceptibility Markers for a Breast-Colon Cancer Phenotype, G8267674335, G8312728332, G8387664760, G8440490342, G8509316824, G9000086995, G9000131883, G9000136306, G9000167908, G9000307018, G9000344111, Cancer Center Support Grant, Cancer Center Support Grant (CCSG), Statistical Methods for Analysis of Massive Genetic and Genomic Data in Cancer Research, G965189902, Effects from Nicotinic Receptor Variations on Smoking Behaviors and Lung Cancer Risk
OpenAlex ID: W2594968232