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| 1 | Comprehensive functional annotation of susceptibility variants identifies genetic heterogeneity between lung adenocarcinoma and squamous cell carcinoma显示文摘Although genome-wide association studies have identified more than eighty genetic variants associated with non-small cell lung cancer(NSCLC)risk,biological mechanisms of these variants remain largely unknown.By integrating a large-scale genotype data of 15581 lung adenocarcinoma(AD)cases,8350 squamous cell carcinoma(SqCC)cases,and 27355 controls,as well as multiple transcriptome and epigenomic databases,we conducted histology-specific meta-analyses and functional annotations of both reported and novel susceptibility variants.We identified 3064 credible risk variants for NSCLC,which were overrepresented in enhancer-like and promoter-like histone modification peaks as well as DNase I hypersensitive sites.Transcription factor enrichment analysis revealed that USF1 was AD-specific while CREB1 was SqCC-specific.Functional annotation and genebased analysis implicated 894 target genes,including 274 specifics for AD and 123 for SqCC,which were overrepresented in somatic driver genes(ER=1.95,P=0.005).Pathway enrichment analysis and Gene-Set Enrichment Analysis revealed that AD genes were primarily involved in immune-related pathways,while SqCC genes were homologous recombination deficiency related.Our results illustrate the molecular basis of both wellstudied and new susceptibility loci of NSCLC,providing not only novel insights into the genetic heterogeneity between AD and SqCC but also a set of plausible gene targets for post-GWAS functional experiments. | Na Qin Yuancheng Li Cheng Wang Meng Zhu Juncheng Dai Tongtong Hong Demetrius Albanes Stephen Lam Adonina Tardon Chu Chen Gary Goodman Stig EBojesen Maria Teresa Landi Mattias Johansson Angela Risch H-Erich Wichmann Heike Bickeboller Gadi Rennert Susanne Arnold Paul Brennan John KField Sanjay Shete Loic Le Marchand Olle Melander Hans Brunnstrom Geoffrey Liu Rayjean JHung Angeline Andrew Lambertus AKiemeney Shan Zienolddiny Kjell Grankvist Mikael Johansson Neil Caporaso Penella Woll Philip Lazarus Matthew BSchabath Melinda CAldrich Victoria LStevens Guangfu Jin David CChristiani Zhibin Hu Christopher IAmos Hongxia Ma Hongbing Shen | 2021 | Frontiers of Medicine2021，15，2： | 3 |
| 2 | Association of the cyclin D1 ,A870G polymorphism with advanced colorectal cancer显示文摘 | Le Marchand L Seifried A Lure -Jones A | 2003 | JAMA2003，290，21： | 1 |
| 3 | Association of the hoGG1 Ser326Cys polymorphism with lung cancer risk显示文摘 | Le Marchand L Donlon T Lum-Jones A | 2002 | Cancer Epidemiol Biomarkers Prev2002，11，4： | 1 |
| 4 | Intake of flavonoids and lung cancer显示文摘 | Le Marchand L Murphy SP Hankin JH | | 0，，： | 1 |
| 5 | A case-control study of diet and colorectal cancer in a multiethnic population in Hawaii ( United States): lipids and foods of animal origin显示文摘 | Le Marchand L Wilkens LR Hankin JH | 1997 | Cancer Causes Control1997，8，4： | 1 |
| 6 | Pooled analysis of the CYP1A1 Exon 7 polymorphism and lung cancer (United States)显示文摘 | Le Marchand L Guo C Benhamou S | 2003 | Cancer Causes and Control2003，14，4： | 1 |
| 7 | Associations of sed- entary lifestyle, obesity, smoking, alcohol use, and diabetes withthe risk of colorectal cancer 显示文摘 | Le Marchand L Wilkens LR Kolonel LN | 1997 | Cancer Rcs1997，57，21： | 1 |
| 8 | Efficient microwave-assisted synthesis of 1-(1 H -indol-1-yl)-2-phenyl-3-(1 H -1,2,4-triazol-1-yl)propan-2-ols as antifungal agents显示文摘 | Nicolas Lebouvier Francis Giraud Typhanie Corbin Young Min Na Guillaume Le Baut Pascal Marchand Marc Le Borgne | 2006 | Tetrahedron Letters2006，，36： | 1 |
| 9 | Genome-wide associationstudies and colorectal cancer 显示文摘 | LE MARCHAND L | 2009 | SurgicalOncology Clinics of North America2009，18，4： | 1 |
| 10 | Vegetable Consumption and Lung Cancer Risk:A Populationbased Case Control Study in Hawaii 显示文摘 | Le Marchand L Yoshizawa CN Colonel LN | 1959 | Natal Cancer Inst1959，51，： | 1 |
| 11 | Association of the hOGG1 Ser326Cys polymorphism with lung cancer risk 显示文摘 | Le Marchand L Donlon T Lum-Jones A | 2002 | Cancer Epidemiol Biomarkers Prev2002，11，： | 1 |
| 12 | Genetic and dietary predictors of CYP2E1 activity:a phenotyping study in Hawaii Japanese using chlorzoxazone显示文摘 | Le Marchand Wilkinson GR Wilkens LR | 1999 | Biomark Prev1999，8，： | 1 |
| 13 | Associations of CYP1A1,GSTM1,and CYP2E1 polymorphisms with lung cancer suggest cell type specificities to tobacco carcinogens显示文摘 | Le Marchand L Sivaraman L Pierce L | 1998 | Cancer-Res1998，58，21： | 1 |
| 14 | Generalizability of associations from prostate cancer genome-wideassociation studies in multiple populations显示文摘 | Waters K M Le Marchand L Kolonel LN | 2009 | Cancer Epidemiol Biomarkers Prev2009，18，4： | 1 |
| 15 | Identification of ractopamine residues in tissue and urine samples at ultra-trace level using liquid chromatography-positive electrospray tandem mass spectrometry 显示文摘 | Antignac J P Marchand P Le Bizec B | 2002 | Journal of Chromatography B:Analytical Technologies in the Biomedical & Life Sciences2002，774，1： | 1 |
| 16 | Intake of flavoids and lung cancer显示文摘 | Le Marchand L Murphg SP Hankin JH | 2000 | J Natl Cancer Inst2000，92，2： | 1 |
| 17 | Prediction of the PCDD/F and dl-PCB 2005-WHO-TEQ content based on the contribution of six congeners: Toward a new screening approach for fish samples?显示文摘 | Ronan Cariou Philippe Marchand Ana?s Vénisseau Aline Brosseaud Dominique Bertrand El Mostafa Qannari Jean-Philippe Antignac Bruno Le Bizec | 2009 | Environmental Pollution2009，，3： | 1 |
| 18 | Association of the my eloperoxidase-463 G→A polymorphism with lung cancer risk 显示文摘 | Le Marchand L Seified A Lum A | 2000 | Cancer Epidemiol Biomarkers Prey2000，9，： | 1 |
| 19 | The MTHFR C677T pol-ymorphism and colorectal cancer:the multiethnic cohort study显示文摘 | Le Marchand L Wilkens LR Kolonel LN | 2005 | Cancer Epidemiol Biomarkers Prev2005，14，5： | 1 |
| 20 | Intake of flavenoids and lung cancer显示文摘 | Loic le marchand SP Murphy JH Hankin LR | 2000 | Journal of the national cancer institute2000，92，2： | 1 |
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