Krista A Zanetti1, Zhaoming Wang2, Melinda Aldrich3, Christopher I Amos4, William J Blot5, Elise D Bowman6, Laurie Burdette7, Qiuyin Cai8, Neil Caporaso9, Charles C Chung10, Elizabeth M Gillanders11, Christopher A Haiman12, Helen M Hansen13, Brian E Henderson14, Laurence N Kolonel15, Loic Le Marchand16, Shengchao Li17, Lorna Haughton McNeill18, Bríd M Ryan19, Ann G Schwartz20, Jennette D Sison21, Margaret R Spitz22, Margaret Tucker23, Angela S Wenzlaff24, John K Wiencke25, Lynne Wilkens26, Margaret R Wrensch27, Xifeng Wu28, Wei Zheng29, Weiyin Zhou30, David Christiani31, Julie R Palmer32, Trevor M Penning33, Alyssa G Rieber34, Lynn Rosenberg35, Edward A Ruiz-Narvaez36, Li Su37, Anil Vachani38, Yongyue Wei39, Alexander S Whitehead40, Stephen J Chanock41, Curtis C Harris42. 1. Division of Cancer Control and Population Sciences, National Cancer Institute, 9609 Medical Center Drive, Rockville, MD 20892, USA. Electronic address: zanettik@mail.nih.gov. 2. Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, Rockville, MD 20892, USA. Electronic address: wangzha@mail.nih.gov. 3. Division of Epidemiology, Vanderbilt University Medical Center, 1161 21st Avenue South, D-3100 Medical Center North, Nashville, TN 37232, USA; Department of Thoracic Surgery, Vanderbilt University Medical Center, 609 Oxford House, 1313 21st Ave South, Nashville, TN 37232-4682, USA. Electronic address: melinda.aldrich@Vanderbilt.Edu. 4. Department of Biomedical Data Science, Geisel School of Medicine, 1 Rope Ferry Road, Dartmouth, Lebanon, NH 03755-1404, USA. Electronic address: Christopher.I.Amos@Dartmouth.edu. 5. Division of Epidemiology, Vanderbilt University Medical Center, 1161 21st Avenue South, D-3100 Medical Center North, Nashville, TN 37232, USA. Electronic address: blotw@iei.us. 6. Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Building 37, Room 3068A, Bethesda, MD 20892, USA. Electronic address: bowmane@intra.nci.nih.gov. 7. Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, Rockville, MD 20892, USA. Electronic address: burdettl@mail.nih.gov. 8. Division of Epidemiology, Vanderbilt University Medical Center, 1161 21st Avenue South, D-3100 Medical Center North, Nashville, TN 37232, USA. Electronic address: qiuyin.cai@Vanderbilt.Edu. 9. Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, Rockville, MD 20892, USA. Electronic address: caporasn@mail.nih.gov. 10. Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, Rockville, MD 20892, USA. Electronic address: chungcc@mail.nih.gov. 11. Division of Cancer Control and Population Sciences, National Cancer Institute, 9609 Medical Center Drive, Rockville, MD 20892, USA. Electronic address: lgilland@mail.nih.gov. 12. Department of Preventive Medicine, Keck School of Medicine, University of Southern California and Norris Comprehensive Cancer Center, 1975 Zonal Avenue, Los Angeles, CA 90033, USA. Electronic address: haiman@usc.edu. 13. Department of Neurological Surgery, University of California, 505 Parnassus Ave., Room 779 M, San Francisco, San Francisco, CA 94143-00112, USA. Electronic address: helen.hansen@ucsf.edu. 14. Department of Preventive Medicine, Keck School of Medicine, University of Southern California and Norris Comprehensive Cancer Center, 1975 Zonal Avenue, Los Angeles, CA 90033, USA. 15. Epidemiology Program, Cancer Research Center, University of Hawaii, 701 Ilalo Street, Honolulu, HI 96813, USA. Electronic address: lkolonel@cc.hawaii.edu. 16. Epidemiology Program, Cancer Research Center, University of Hawaii, 701 Ilalo Street, Honolulu, HI 96813, USA. Electronic address: Loic@cc.hawaii.edu. 17. Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, Rockville, MD 20892, USA. Electronic address: shengchao.li@nih.gov. 18. Department of Health Disparities Research, Division of OVP, Cancer Prevention and Population Sciences, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 91, Houston, TX 77030, USA. Electronic address: lmcneill@mdanderson.org. 19. Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Building 37, Room 3068A, Bethesda, MD 20892, USA. Electronic address: ryanb@mail.nih.gov. 20. Department of Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine, 4100 John R, Detroit, MI 48201, USA. Electronic address: schwarta@karmanos.org. 21. Department of Neurological Surgery, University of California, 505 Parnassus Ave., Room 779 M, San Francisco, San Francisco, CA 94143-00112, USA. Electronic address: jennette.sison@ucsf.edu. 22. Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Mail Stop BCM225, Houston, TX 77030, USA. Electronic address: spitz@bcm.edu. 23. Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, Rockville, MD 20892, USA. Electronic address: tuckerp@mail.nih.gov. 24. Department of Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine, 4100 John R, Detroit, MI 48201, USA. Electronic address: wenzlaff@karmanos.org. 25. Department of Neurological Surgery, University of California, 505 Parnassus Ave., Room 779 M, San Francisco, San Francisco, CA 94143-00112, USA. Electronic address: john.wiencke@ucsf.edu. 26. Epidemiology Program, Cancer Research Center, University of Hawaii, 701 Ilalo Street, Honolulu, HI 96813, USA. Electronic address: lynne@cc.hawaii.edu. 27. Department of Neurological Surgery, University of California, 505 Parnassus Ave., Room 779 M, San Francisco, San Francisco, CA 94143-00112, USA. Electronic address: Margaret.Wrensch@ucsf.edu. 28. Department of Epidemiology, Division of OVP, Cancer Prevention and Population Sciences, The University of Texas MD Anderson Cancer Center, Unit 1340, PO Box 301439, Houston, TX 77230-1439, USA. Electronic address: xwu@mdanderson.org. 29. Division of Epidemiology, Vanderbilt University Medical Center, 1161 21st Avenue South, D-3100 Medical Center North, Nashville, TN 37232, USA. Electronic address: wei.zheng@vanderbilt.edu. 30. Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, Rockville, MD 20892, USA. Electronic address: zhouw@mail.nih.gov. 31. Harvard School of Public Health, Massachusetts General Hospital/Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA. Electronic address: dchris@hsph.harvard.edu. 32. Slone Epidemiology Cancer Center at Boston University, 1010 Commonwealth Avenue, 4th Floor, Boston, MA 02215, USA. Electronic address: jpalmer@bu.edu. 33. Center of Excellence in Environmental Toxicology, Perelman School of Medicine, University of Pennsylvania, 3535 Market Street, Mezzanine, Philadelphia PA 19104, USA; Department of Pharmacology, Perelman School of Medicine, University of Pennsylvania, 3535 Market Street, Mezzanine, Philadelphia PA 19104, USA. Electronic address: PENNING@UPENN.EDU. 34. Department of General Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA. Electronic address: arieber@mdanderson.org. 35. Slone Epidemiology Cancer Center at Boston University, 1010 Commonwealth Avenue, 4th Floor, Boston, MA 02215, USA. Electronic address: lrosenbe@bu.edu. 36. Slone Epidemiology Cancer Center at Boston University, 1010 Commonwealth Avenue, 4th Floor, Boston, MA 02215, USA. Electronic address: eruiznar@bu.edu. 37. Harvard School of Public Health, Massachusetts General Hospital/Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA. Electronic address: lisu@hsph.harvard.edu. 38. Center of Excellence in Environmental Toxicology, Perelman School of Medicine, University of Pennsylvania, 3535 Market Street, Mezzanine, Philadelphia PA 19104, USA; Department of Medicine, Perelman School of Medicine, University of Pennsylvania, 3535 Market Street, Mezzanine, Philadelphia, PA 19104, USA. Electronic address: avachani@mail.med.upenn.edu. 39. Harvard School of Public Health, Massachusetts General Hospital/Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA. Electronic address: ywei@hsph.harvard.edu. 40. Center of Excellence in Environmental Toxicology, Perelman School of Medicine, University of Pennsylvania, 3535 Market Street, Mezzanine, Philadelphia PA 19104, USA; Department of Pharmacology, Perelman School of Medicine, University of Pennsylvania, 3535 Market Street, Mezzanine, Philadelphia PA 19104, USA. Electronic address: aswhiteh@mail.med.upenn.edu. 41. Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, Rockville, MD 20892, USA. Electronic address: chanocks@mail.nih.gov. 42. Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Building 37, Room 3068A, Bethesda, MD 20892, USA. Electronic address: Curtis_Harris@nih.gov.
Abstract
OBJECTIVES: Genome-wide association studies (GWAS) of lung cancer have identified regions of common genetic variation with lung cancer risk in Europeans who smoke and never-smoking Asian women. This study aimed to conduct a GWAS in African Americans, who have higher rates of lung cancer despite smoking fewer cigarettes per day when compared with Caucasians. This population provides a different genetic architecture based on underlying African ancestry allowing the identification of new regions and exploration of known regions for finer mapping. MATERIALS AND METHODS: We genotyped 1,024,001 SNPs in 1737 cases and 3602 controls in stage 1, followed by a replication phase of 20 SNPs (p<1.51×10(-5)) in an independent set of 866 cases and 796 controls in stage 2. RESULTS AND CONCLUSION: In the combined analysis, we confirmed two loci to be associated with lung cancer that achieved the threshold of genome-wide significance: 15q25.1 marked by rs2036527 (p=1.3×10(-9); OR=1.32; 95% CI=1.20-1.44) near CHRNA5, and 5p15.33 marked by rs2853677 (p=2.8×10(-9); OR=1.28; 95% CI=1.18-1.39) near TERT. The association with rs2853677 is driven by the adenocarcinoma subtype of lung cancer (p=1.3×10(-8); OR=1.37; 95% CI=1.23-1.54). No SNPs reached genome-wide significance for either of the main effect models examining smoking - cigarettes per day and current or former smoker. Our study was powered to identify strong risk loci for lung cancer in African Americans; we confirmed results previously reported in African Americans and other populations for two loci near plausible candidate genes, CHRNA5 and TERT, on 15q25.1 and 5p15.33 respectively, are associated with lung cancer. Additional work is required to map and understand the biological underpinnings of the strong association of these loci with lung cancer risk in African Americans. Published by Elsevier Ireland Ltd.
OBJECTIVES: Genome-wide association studies (GWAS) of lung cancer have identified regions of common genetic variation with lung cancer risk in Europeans who smoke and never-smoking Asian women. This study aimed to conduct a GWAS in African Americans, who have higher rates of lung cancer despite smoking fewer cigarettes per day when compared with Caucasians. This population provides a different genetic architecture based on underlying African ancestry allowing the identification of new regions and exploration of known regions for finer mapping. MATERIALS AND METHODS: We genotyped 1,024,001 SNPs in 1737 cases and 3602 controls in stage 1, followed by a replication phase of 20 SNPs (p<1.51×10(-5)) in an independent set of 866 cases and 796 controls in stage 2. RESULTS AND CONCLUSION: In the combined analysis, we confirmed two loci to be associated with lung cancer that achieved the threshold of genome-wide significance: 15q25.1 marked by rs2036527 (p=1.3×10(-9); OR=1.32; 95% CI=1.20-1.44) near CHRNA5, and 5p15.33 marked by rs2853677 (p=2.8×10(-9); OR=1.28; 95% CI=1.18-1.39) near TERT. The association with rs2853677 is driven by the adenocarcinoma subtype of lung cancer (p=1.3×10(-8); OR=1.37; 95% CI=1.23-1.54). No SNPs reached genome-wide significance for either of the main effect models examining smoking - cigarettes per day and current or former smoker. Our study was powered to identify strong risk loci for lung cancer in African Americans; we confirmed results previously reported in African Americans and other populations for two loci near plausible candidate genes, CHRNA5 and TERT, on 15q25.1 and 5p15.33 respectively, are associated with lung cancer. Additional work is required to map and understand the biological underpinnings of the strong association of these loci with lung cancer risk in African Americans. Published by Elsevier Ireland Ltd.
Authors: Richard Sherva; Henry R Kranzler; Yi Yu; Mark W Logue; James Poling; Albert J Arias; Raymond F Anton; David Oslin; Lindsay A Farrer; Joel Gelernter Journal: Neuropsychopharmacology Date: 2010-05-19 Impact factor: 7.853
Authors: Li-Shiun Chen; Nancy L Saccone; Robert C Culverhouse; Paige M Bracci; Chien-Hsiun Chen; Nicole Dueker; Younghun Han; Hongyan Huang; Guangfu Jin; Takashi Kohno; Jennie Z Ma; Thomas R Przybeck; Alan R Sanders; Jennifer A Smith; Yun Ju Sung; Angie S Wenzlaff; Chen Wu; Dankyu Yoon; Ying-Ting Chen; Yu-Ching Cheng; Yoon Shin Cho; Sean P David; Jubao Duan; Charles B Eaton; Helena Furberg; Alison M Goate; Dongfeng Gu; Helen M Hansen; Sarah Hartz; Zhibin Hu; Young Jin Kim; Steven J Kittner; Douglas F Levinson; Thomas H Mosley; Thomas J Payne; D C Rao; John P Rice; Treva K Rice; Tae-Hwi Schwantes-An; Sanjay S Shete; Jianxin Shi; Margaret R Spitz; Yan V Sun; Fuu-Jen Tsai; Jen C Wang; Margaret R Wrensch; Hong Xian; Pablo V Gejman; Jiang He; Steven C Hunt; Sharon L Kardia; Ming D Li; Dongxin Lin; Braxton D Mitchell; Taesung Park; Ann G Schwartz; Hongbing Shen; John K Wiencke; Jer-Yuarn Wu; Jun Yokota; Christopher I Amos; Laura J Bierut Journal: Genet Epidemiol Date: 2012-05 Impact factor: 2.135
Authors: Richard A Grucza; Eric O Johnson; Robert F Krueger; Naomi Breslau; Nancy L Saccone; Li-Shiun Chen; Jaime Derringer; Arpana Agrawal; Michael Lynskey; Laura J Bierut Journal: Addict Biol Date: 2010-07 Impact factor: 4.280
Authors: Nancy L Saccone; Robert C Culverhouse; Tae-Hwi Schwantes-An; Dale S Cannon; Xiangning Chen; Sven Cichon; Ina Giegling; Shizhong Han; Younghun Han; Kaisu Keskitalo-Vuokko; Xiangyang Kong; Maria Teresa Landi; Jennie Z Ma; Susan E Short; Sarah H Stephens; Victoria L Stevens; Lingwei Sun; Yufei Wang; Angela S Wenzlaff; Steven H Aggen; Naomi Breslau; Peter Broderick; Nilanjan Chatterjee; Jingchun Chen; Andrew C Heath; Markku Heliövaara; Nicole R Hoft; David J Hunter; Majken K Jensen; Nicholas G Martin; Grant W Montgomery; Tianhua Niu; Thomas J Payne; Leena Peltonen; Michele L Pergadia; John P Rice; Richard Sherva; Margaret R Spitz; Juzhong Sun; Jen C Wang; Robert B Weiss; William Wheeler; Stephanie H Witt; Bao-Zhu Yang; Neil E Caporaso; Marissa A Ehringer; Tim Eisen; Susan M Gapstur; Joel Gelernter; Richard Houlston; Jaakko Kaprio; Kenneth S Kendler; Peter Kraft; Mark F Leppert; Ming D Li; Pamela A F Madden; Markus M Nöthen; Sreekumar Pillai; Marcella Rietschel; Dan Rujescu; Ann Schwartz; Christopher I Amos; Laura J Bierut Journal: PLoS Genet Date: 2010-08-05 Impact factor: 5.917
Authors: Goncalo R Abecasis; Adam Auton; Lisa D Brooks; Mark A DePristo; Richard M Durbin; Robert E Handsaker; Hyun Min Kang; Gabor T Marth; Gil A McVean Journal: Nature Date: 2012-11-01 Impact factor: 49.962
Authors: S P David; A Hamidovic; G K Chen; A W Bergen; J Wessel; J L Kasberger; W M Brown; S Petruzella; E L Thacker; Y Kim; M A Nalls; G J Tranah; Y J Sung; C B Ambrosone; D Arnett; E V Bandera; D M Becker; L Becker; S I Berndt; L Bernstein; W J Blot; U Broeckel; S G Buxbaum; N Caporaso; G Casey; S J Chanock; S L Deming; W R Diver; C B Eaton; D S Evans; M K Evans; M Fornage; N Franceschini; T B Harris; B E Henderson; D G Hernandez; B Hitsman; J J Hu; S C Hunt; S A Ingles; E M John; R Kittles; S Kolb; L N Kolonel; L Le Marchand; Y Liu; K K Lohman; B McKnight; R C Millikan; A Murphy; C Neslund-Dudas; S Nyante; M Press; B M Psaty; D C Rao; S Redline; J L Rodriguez-Gil; B A Rybicki; L B Signorello; A B Singleton; J Smoller; B Snively; B Spring; J L Stanford; S S Strom; G E Swan; K D Taylor; M J Thun; A F Wilson; J S Witte; Y Yamamura; L R Yanek; K Yu; W Zheng; R G Ziegler; A B Zonderman; E Jorgenson; C A Haiman; H Furberg Journal: Transl Psychiatry Date: 2012-05-22 Impact factor: 6.222
Authors: Richard Sherva; Kirk Wilhelmsen; Cynthia S Pomerleau; Scott A Chasse; John P Rice; Sandy M Snedecor; Laura J Bierut; Rosalind J Neuman; Ovide F Pomerleau Journal: Addiction Date: 2008-09 Impact factor: 6.526
Authors: Donovan Watza; Christine M Lusk; Gregory Dyson; Kristen S Purrington; Angela S Wenzlaff; Christine Neslund-Dudas; Ayman O Soubani; Shirish M Gadgeel; Ann G Schwartz Journal: Int J Cancer Date: 2019-12-12 Impact factor: 7.396
Authors: Khadijah A Mitchell; Ebony Shah; Elise D Bowman; Adriana Zingone; Noah Nichols; Sharon R Pine; Rick A Kittles; Bríd M Ryan Journal: Cancer Causes Control Date: 2019-08-29 Impact factor: 2.506
Authors: Carissa C Jones; Yuki Bradford; Christopher I Amos; William J Blot; Stephen J Chanock; Curtis C Harris; Ann G Schwartz; Margaret R Spitz; John K Wiencke; Margaret R Wrensch; Xifeng Wu; Melinda C Aldrich Journal: Cancer Epidemiol Biomarkers Prev Date: 2019-03-20 Impact factor: 4.254
Authors: Jinyoung Byun; Younghun Han; Yafang Li; Jun Xia; Erping Long; Jiyeon Choi; Xiangjun Xiao; Meng Zhu; Wen Zhou; Ryan Sun; Yohan Bossé; Zhuoyi Song; Ann Schwartz; Christine Lusk; Thorunn Rafnar; Kari Stefansson; Tongwu Zhang; Wei Zhao; Rowland W Pettit; Yanhong Liu; Xihao Li; Hufeng Zhou; Kyle M Walsh; Ivan Gorlov; Olga Gorlova; Dakai Zhu; Susan M Rosenberg; Susan Pinney; Joan E Bailey-Wilson; Diptasri Mandal; Mariza de Andrade; Colette Gaba; James C Willey; Ming You; Marshall Anderson; John K Wiencke; Demetrius Albanes; Stephan Lam; Adonina Tardon; Chu Chen; Gary Goodman; Stig Bojeson; Hermann Brenner; Maria Teresa Landi; Stephen J Chanock; Mattias Johansson; Thomas Muley; Angela Risch; H-Erich Wichmann; Heike Bickeböller; David C Christiani; Gad Rennert; Susanne Arnold; John K Field; Sanjay Shete; Loic Le Marchand; Olle Melander; Hans Brunnstrom; Geoffrey Liu; Angeline S Andrew; Lambertus A Kiemeney; Hongbing Shen; Shanbeh Zienolddiny; Kjell Grankvist; Mikael Johansson; Neil Caporaso; Angela Cox; Yun-Chul Hong; Jian-Min Yuan; Philip Lazarus; Matthew B Schabath; Melinda C Aldrich; Alpa Patel; Qing Lan; Nathaniel Rothman; Fiona Taylor; Linda Kachuri; John S Witte; Lori C Sakoda; Margaret Spitz; Paul Brennan; Xihong Lin; James McKay; Rayjean J Hung; Christopher I Amos Journal: Nat Genet Date: 2022-08-01 Impact factor: 41.307
Authors: Khadijah A Mitchell; Adriana Zingone; Leila Toulabi; Jacob Boeckelman; Bríd M Ryan Journal: Clin Cancer Res Date: 2017-12-01 Impact factor: 12.531
Authors: Ewoud Schuit; Orestis A Panagiotou; Marcus R Munafò; Derrick A Bennett; Andrew W Bergen; Sean P David Journal: Cochrane Database Syst Rev Date: 2017-09-08