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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Genome-wide association meta-analysis identifies pleiotropic risk loci for aerodigestive squamous cell cancers

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Autor(es):
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Lesseur, Corina [1, 2] ; Ferreiro-Iglesias, Aida [1] ; McKay, James D. [3] ; Bosse, Yohan [4] ; Johansson, Mattias [1] ; Gaborieau, Valerie [1] ; Landi, Maria Teresa [5] ; Christiani, David C. [6] ; Caporaso, Neil C. [5] ; Bojesen, Stig E. [7] ; Amos, Christopher I. [8] ; Shete, Sanjay [9] ; Liu, Geoffrey [10] ; Rennert, Gadi [11] ; Albanes, Demetrios [5] ; Aldrich, Melinda C. [12] ; Tardon, Adonina [13, 14] ; Chen, Chu [15] ; Triantafillos, Liloglou [16] ; Field, John K. [16] ; Teare, Marion Dawn [17] ; Kiemeney, Lambertus A. [18] ; Diergaarde, Brenda [19, 20, 21] ; Ferris, Robert L. [20] ; Zienolddiny, Shanbeh [22] ; Lam, Stephen [23] ; Olshan, Andrew F. [24] ; Weissler, Mark C. [25] ; Lacko, Martin [26] ; Risch, Angela [27, 28, 29, 30] ; Bickeboller, Heike [31] ; Ness, Andy R. [32, 33] ; Thomas, Steve [33] ; Le Marchand, Loic [34] ; Schabath, Matthew B. [35] ; Wunsch-Filho, Victor [36] ; Tajara, Eloiza H. [37] ; Andrew, Angeline S. [38] ; Clifford, Gary M. [39] ; Lazarus, Philip [40] ; Grankvist, Kjell [41] ; Johansson, Mikael [42] ; Arnold, Susanne [43] ; Melander, Olle [44, 45] ; Brunnstrom, Hans [46] ; Boccia, Stefania [47, 48] ; Cadoni, Gabriella [49, 50] ; Timens, Wim [51, 52] ; Obeidat, Ma'en [53] ; Xiao, Xiangjun [8] ; Houlston, Richard S. [54] ; Hung, Rayjean J. [55] ; Brennan, Paul [1]
Número total de Autores: 53
Afiliação do(s) autor(es):
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[1] World Hlth Org, Sect Genet, Genet Epidmiol Grp, Int Agcy Res Canc, Lyon - France
[2] Icahn Sch Med Mt Sinai, Dept Environm Med & Publ Hlth, New York, NY 10029 - USA
[3] World Hlth Org, Sect Genet, Genet Canc Susceptibil Grp, Int Agcy Res Canc, Lyon - France
[4] Laval Univ, Inst Univ Cardiol Pneumol Quebec, Dept Mol Med, Quebec City, PQ - Canada
[5] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 - USA
[6] Massachusetts Gen Hosp, Harvard TH Chan Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02114 - USA
[7] Herlev & Gentofte Hosp, Copenhagen Gen Populat Study, Copenhagen - Denmark
[8] Baylor Coll Med, Dept Med, Houston, TX 77030 - USA
[9] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 - USA
[10] Univ Toronto, Tanenbaum Res Inst Sinai Hlth Syst, Toronto, ON - Canada
[11] Technion Fac Med, Clalit Natl Canc Control Ctr, Carmel Med Ctr, Haifa - Israel
[12] Vanderbilt Univ, Dept Thorac Surg, Div Epidmiol, Med Ctr, Nashville, TN - USA
[13] Univ Oviedo, Fac Med, Oviedo - Spain
[14] CIBERESP, Oviedo - Spain
[15] Univ Washington, Dept Epidmiol, Sch Publ Hlth & Community Med, Seattle, WA 98195 - USA
[16] Univ Liverpool, Inst Translat Med, Liverpool, Merseyside - England
[17] Univ Sheffield, Sch Hlth & Related Res, Sheffield, S Yorkshire - England
[18] Radboud Univ Nijmegen, Med Ctr, Nijmegen - Netherlands
[19] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA - USA
[20] Univ Pittsburgh, UPMC Hillman Canc Ctr, Pittsburgh, PA - USA
[21] Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA - USA
[22] Natl Inst Occupat Hlth, Oslo - Norway
[23] British Columbia Canc Agcy, Vancouver, BC - Canada
[24] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Epidmiol, Chapel Hill, NC - USA
[25] Univ North Carolina Chapel Hill, UNC Lineberger Comprehens Canc Ctr, Dept Otolaryngol Head & Neck Surg, Chapel Hill, NC - USA
[26] Maastricht Univ, Dept Otorhinolaryngol Head & Neck Surg, Med Ctr, Maastricht - Netherlands
[27] Univ Salzburg, Dept Biosci & Canc Cluster Salzburg, Salzburg - Austria
[28] DKFZ German Canc Res Ctr, Div Epign, Heidelberg - Germany
[29] Translat Lung Res Ctr Heidelberg TLRC H, Heidelberg - Germany
[30] German Ctr Lung Res DZL, Heidelberg - Germany
[31] Georg August Univ Gottingen, Univ Med Ctr, Dept Genet Epidmiol, Gottingen - Germany
[32] Univ Hosp Bristol NHS Fdn Trust, Natl Inst Hlth Res, Bristol Biomed Res Ctr, NIHR, Bristol, Avon - England
[33] Univ Bristol, Bristol Dent Sch, Bristol, Avon - England
[34] Univ Hawaii, Ctr Canc, Honolulu, HI 96822 - USA
[35] H Lee Moffitt Canc Ctr & Res Inst, Dept Canc Epidemiol, Tampa, FL - USA
[36] Univ Sao Paulo, Fac Saude Publ, Sao Paulo - Brazil
[37] Sch Med Sao Jose Rio Preto, Dept Mol Biol, Sao Jose Do Rio Preto - Brazil
[38] Dartmouth Coll, Biomed Data Sci, Geisel Sch Med Dartmouth, Hanover, NH 03755 - USA
[39] World Hlth Org, Infect Sect, Infect & Canc Epidmiol Grp, Int Agcy Res Canc, Lyon - France
[40] Washington State Univ, Coll Pharm, Dept Pharmaceut Sci, Spokane, WA - USA
[41] Umea Univ, Dept Med Biosci, Umea - Sweden
[42] Umea Univ, Dept Radiat Sci, Umea - Sweden
[43] Univ Kentucky, Markey Canc Ctr, Lexington, KY - USA
[44] Lund Univ, Dept Clin Sci Malmo, Malmo - Sweden
[45] Skane Univ Hosp, Dept Internal Med, Malmo - Sweden
[46] Lund Univ, Dept Clin Sci, Lund - Sweden
[47] Univ Cattolica Sacro Cuore, Univ Dept Life Sci & Publ Hlth, Sect Hyg, Rome - Italy
[48] Fdn Policlin Univ, Dipartimento Sci Invecchiamento Neurol, Gemelli IRCCS, Ortopedi Testa, Rome - Italy
[49] Fdn Policlin Univ A Gemelli IRCCS, Dipartimento Sci Invecchiamento Neurol Ortoped &, Rome - Italy
[50] Univ Cattolica Sacro Cuore, Ist Clin Otrinlaringiatr, Dipartimento Patol Testa Collo & Organi Senso, Rome - Italy
[51] Univ Groningen, Univ Med Ctr Groningen, Dept Pathol & Med Biol, Groningen - Netherlands
[52] Univ Groningen, GRIAC Res Inst, Groningen - Netherlands
[53] Univ British Columbia, St Pauls Hosp, Ctr Heart Lung Innovat, Vancouver, BC - Canada
[54] Inst Canc Res, Div Genet & Epidmiol, London - England
[55] Sinai Hlth Syst, Prosserman Ctr Populat Hlth Res, Lunenfeld Tanenbaum Res Inst, Toronto, ON - Canada
Número total de Afiliações: 55
Tipo de documento: Artigo Científico
Fonte: PLOS GENETICS; v. 17, n. 3 MAR 2021.
Citações Web of Science: 0
Resumo

Squamous cell carcinomas (SqCC) of the aerodigestive tract have similar etiological risk factors. Although genetic risk variants for individual cancers have been identified, an agnostic, genome-wide search for shared genetic susceptibility has not been performed. To identify novel and pleotropic SqCC risk variants, we performed a meta-analysis of GWAS data on lung SqCC (LuSqCC), oro/pharyngeal SqCC (OSqCC), laryngeal SqCC (LaSqCC) and esophageal SqCC (ESqCC) cancers, totaling 13,887 cases and 61,961 controls of European ancestry. We identified one novel genome-wide significant (P-meta<5x10(-8)) aerodigestive SqCC susceptibility loci in the 2q33.1 region (rs56321285, TMEM273). Additionally, three previously unknown loci reached suggestive significance (P-meta<5x10(-7)): 1q32.1 (rs12133735, near MDM4), 5q31.2 (rs13181561, TMEM173) and 19p13.11 (rs61494113, ABHD8). Multiple previously identified loci for aerodigestive SqCC also showed evidence of pleiotropy in at least another SqCC site, these include: 4q23 (ADH1B), 6p21.33 (STK19), 6p21.32 (HLA-DQB1), 9p21.33 (CDKN2B-AS1) and 13q13.1(BRCA2). Gene-based association and gene set enrichment identified a set of 48 SqCC-related genes to DNA damage and epigenetic regulation pathways. Our study highlights the importance of cross-cancer analyses to identify pleiotropic risk loci of histology-related cancers arising at distinct anatomical sites. Author summary Squamous cell carcinomas are specific type of cancer that can arise in multiple organs of the aerodigestive tract including the lung, oral cavity, oropharynx, larynx and esophagus. Previous studies have shown that aerodigestive squamous cell carcinomas share common environmental risk factors (tobacco smoking and alcohol intake). Here, we investigate genetic factors involved in the risk of aerodigestive squamous cell carcinomas as a group in a large genetic association study involving 13,887 cancer cases and 61,961 controls. We identified one genome-wide significant region within 2q33.1 and 3 other suggestive regions at 1q32.1, 5q31.2 and 19p13.11. Gene-based analyses also identify a list of SqCC-related genes that are involved in DNA damage response and epigenetic regulation. Our results suggest some overlap in the genetic factors influencing the risk of aerodigestive squamous cell carcinomas in European populations and highlights the importance of cross-cancer studies. (AU)

Processo FAPESP: 10/51168-0 - Fatores ambientais, clínicos, histopatológicos e moleculares associados ao desenvolvimento e ao prognóstico de carcinomas epidermoides de cabeça e pescoço
Beneficiário:Eloiza Helena Tajara da Silva
Linha de fomento: Auxílio à Pesquisa - Temático
Processo FAPESP: 04/12054-9 - Busca de marcadores de agressividade em tumores de cabeça e pescoço
Beneficiário:Eloiza Helena Tajara da Silva
Linha de fomento: Auxílio à Pesquisa - Temático