Genome-wide association analyses identify new susceptibility loci for oral cavity and pharyngeal cancer.

2.50
Hdl Handle:
http://hdl.handle.net/10146/618164
Title:
Genome-wide association analyses identify new susceptibility loci for oral cavity and pharyngeal cancer.
Authors:
Lesseur, Corina; Diergaarde, Brenda; Olshan, Andrew F; Wünsch-Filho, Victor; Ness, Andrew R; Liu, Geoffrey; Lacko, Martin; Eluf-Neto, José; Franceschi, Silvia; Lagiou, Pagona; Macfarlane, Gary J; Richiardi, Lorenzo; Boccia, Stefania; Polesel, Jerry; Kjaerheim, Kristina; Zaridze, David; Johansson, Mattias; Menezes, Ana M; Curado, Maria Paula; Robinson, Max; Ahrens, Wolfgang; Canova, Cristina; Znaor, Ariana; Castellsagué, Xavier; Conway, David I; Holcátová, Ivana; Mates, Dana; Vilensky, Marta; Healy, Claire M; Szeszenia-Dabrowska, Neonila ( 0000-0001-5307-7720 ) ; Fabiánová, Eleonóra; Lissowska, Jolanta; Grandis, Jennifer R; Weissler, Mark C; Tajara, Eloiza H; Nunes, Fabio D; de Carvalho, Marcos B; Thomas, Steve; Hung, Rayjean J; Peters, Wilbert H M; Herrero, Rolando; Cadoni, Gabriella; Bueno-de-Mesquita, H Bas; Steffen, Annika; Agudo, Antonio; Shangina, Oxana; Xiao, Xiangjun; Gaborieau, Valérie; Chabrier, Amélie; Anantharaman, Devasena; Boffetta, Paolo; Amos, Christopher I; McKay, James D; Brennan, Paul
Abstract:
We conducted a genome-wide association study of oral cavity and pharyngeal cancer in 6,034 cases and 6,585 controls from Europe, North America and South America. We detected eight significantly associated loci (P < 5 × 10(-8)), seven of which are new for these cancer sites. Oral and pharyngeal cancers combined were associated with loci at 6p21.32 (rs3828805, HLA-DQB1), 10q26.13 (rs201982221, LHPP) and 11p15.4 (rs1453414, OR52N2-TRIM5). Oral cancer was associated with two new regions, 2p23.3 (rs6547741, GPN1) and 9q34.12 (rs928674, LAMC3), and with known cancer-related loci-9p21.3 (rs8181047, CDKN2B-AS1) and 5p15.33 (rs10462706, CLPTM1L). Oropharyngeal cancer associations were limited to the human leukocyte antigen (HLA) region, and classical HLA allele imputation showed a protective association with the class II haplotype HLA-DRB1*1301-HLA-DQA1*0103-HLA-DQB1*0603 (odds ratio (OR) = 0.59, P = 2.7 × 10(-9)). Stratified analyses on a subgroup of oropharyngeal cases with information available on human papillomavirus (HPV) status indicated that this association was considerably stronger in HPV-positive (OR = 0.23, P = 1.6 × 10(-6)) than in HPV-negative (OR = 0.75, P = 0.16) cancers.
Affiliation:
Nofer Institute of Occupational Medicine, Łódź, Poland
Citation:
Nat. Genet. 2016, 48 (12):1544-1550
Journal:
Nature Genetics
Issue Date:
Dec-2016
URI:
http://hdl.handle.net/10146/618164
DOI:
10.1038/ng.3685
PubMed ID:
27749845
Additional Links:
https://www.nature.com/ng/journal/v48/n12/full/ng.3685.html
Type:
Article
Language:
en
ISSN:
1546-1718
Sponsors:
Genotyping performed at the Center for Inherited Disease Research (CIDR) was funded through the U.S. National Institute of Dental and Craniofacial Research (NIDCR) grant 1X01HG007780-0. Genotyping for shared controls with the Lung OncoArray initiative was funded through the grant X01HG007492-0. Corina Lesseur undertook this work during the tenure of a Postdoctoral Fellowship awarded by the International Agency for Research on Cancer. The funders did not participate in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. We acknowledge all of the participants involved in this research and the funders and support. We thank Dr. Leticia Fernandez (Instituto Nacional de Oncologia y Radiobiologia, La Habana, Cuba) for her contribution to the IARC ORC multicenter study. We are also grateful to Sergio Koifman (Escola Nacional de Saúde Pública, Rio de Janeiro, Brazil) for his contribution to the IARC Latin America multicenter study (Sergio Koifman passed away in May 2014) and to Xavier Castellsagué from the ARCAGE Barcelona Center who recently passed away (June 2016). The University of Pittsburgh head and neck cancer case-control study is supported by National Institutes of Health grants P50 CA097190 and P30 CA047904. The Carolina Head and Neck Cancer Study (CHANCE) was supported by the National Cancer Institute (R01-CA90731). The Head and Neck Genome Project (GENCAPO) was supported by the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) (Grant numbers 04/12054-9 and 10/51168-0). The authors thank all the members of the GENCAPO team. The HN5000 study was funded by the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research scheme (RP-PG-0707-10034), the views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. The Toronto study was funded by the Canadian Cancer Society Research Institute (020214) and the National Cancer Institute (U19 CA148127) and the Cancer Care Ontario Research Chair. The alcohol-related cancers and genetic susceptibility study in Europe (ARCAGE) was funded by the European Commission’s 5th Framework Program (QLK1-2001-00182), the Italian Association for Cancer Research, Compagnia di San Paolo/FIRMS, Region Piemonte, and Padova University (CPDA057222).The Rome Study was supported by the Associazione Italiana per la Ricerca sul Cancro (AIRC) IG 2011 10491 and IG2013 14220 to SB, and Fondazione Veronesi to SB. The IARC Latin American study was funded by the European Commission INCO-DC programme (IC18-CT97-0222), with additional funding from Fondo para la Investigacion Cientifica y Tecnologica (Argentina) and the Fundação de Amparo à Pesquisa do Estado de São Paulo (01/01768-2). The IARC Central Europe study was supported by European Commission’s INCO-COPERNICUS Program (IC15-CT98-0332), NIH/National Cancer Institute grant CA92039, and the World Cancer Research Foundation grant WCRF 99A28.The IARC Oral Cancer Multicenter study was funded by: grant S06 96 202489 05F02 from Europe against Cancer; Grants FIS 97/0024, FIS 97/0662, and BAE 01/5013 from Fondo de Investigaciones Sanitarias, Spain; UICC Yamagiwa-Yoshida Memorial International Cancer Study; National Cancer Institute of Canada; Italian Association for Research on Cancer; and the Pan American Health Organization. The coordination of EPIC study is financially supported
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DC FieldValue Language
dc.contributor.authorLesseur, Corinaen
dc.contributor.authorDiergaarde, Brendaen
dc.contributor.authorOlshan, Andrew Fen
dc.contributor.authorWünsch-Filho, Victoren
dc.contributor.authorNess, Andrew Ren
dc.contributor.authorLiu, Geoffreyen
dc.contributor.authorLacko, Martinen
dc.contributor.authorEluf-Neto, Joséen
dc.contributor.authorFranceschi, Silviaen
dc.contributor.authorLagiou, Pagonaen
dc.contributor.authorMacfarlane, Gary Jen
dc.contributor.authorRichiardi, Lorenzoen
dc.contributor.authorBoccia, Stefaniaen
dc.contributor.authorPolesel, Jerryen
dc.contributor.authorKjaerheim, Kristinaen
dc.contributor.authorZaridze, Daviden
dc.contributor.authorJohansson, Mattiasen
dc.contributor.authorMenezes, Ana Men
dc.contributor.authorCurado, Maria Paulaen
dc.contributor.authorRobinson, Maxen
dc.contributor.authorAhrens, Wolfgangen
dc.contributor.authorCanova, Cristinaen
dc.contributor.authorZnaor, Arianaen
dc.contributor.authorCastellsagué, Xavieren
dc.contributor.authorConway, David Ien
dc.contributor.authorHolcátová, Ivanaen
dc.contributor.authorMates, Danaen
dc.contributor.authorVilensky, Martaen
dc.contributor.authorHealy, Claire Men
dc.contributor.authorSzeszenia-Dabrowska, Neonilaen
dc.contributor.authorFabiánová, Eleonóraen
dc.contributor.authorLissowska, Jolantaen
dc.contributor.authorGrandis, Jennifer Ren
dc.contributor.authorWeissler, Mark Cen
dc.contributor.authorTajara, Eloiza Hen
dc.contributor.authorNunes, Fabio Den
dc.contributor.authorde Carvalho, Marcos Ben
dc.contributor.authorThomas, Steveen
dc.contributor.authorHung, Rayjean Jen
dc.contributor.authorPeters, Wilbert H Men
dc.contributor.authorHerrero, Rolandoen
dc.contributor.authorCadoni, Gabriellaen
dc.contributor.authorBueno-de-Mesquita, H Basen
dc.contributor.authorSteffen, Annikaen
dc.contributor.authorAgudo, Antonioen
dc.contributor.authorShangina, Oxanaen
dc.contributor.authorXiao, Xiangjunen
dc.contributor.authorGaborieau, Valérieen
dc.contributor.authorChabrier, Amélieen
dc.contributor.authorAnantharaman, Devasenaen
dc.contributor.authorBoffetta, Paoloen
dc.contributor.authorAmos, Christopher Ien
dc.contributor.authorMcKay, James Den
dc.contributor.authorBrennan, Paulen
dc.date.accessioned2017-10-20T07:56:05Z-
dc.date.available2017-10-20T07:56:05Z-
dc.date.issued2016-12-
dc.identifier.citationNat. Genet. 2016, 48 (12):1544-1550en
dc.identifier.issn1546-1718-
dc.identifier.pmid27749845-
dc.identifier.doi10.1038/ng.3685-
dc.identifier.urihttp://hdl.handle.net/10146/618164-
dc.description.abstractWe conducted a genome-wide association study of oral cavity and pharyngeal cancer in 6,034 cases and 6,585 controls from Europe, North America and South America. We detected eight significantly associated loci (P < 5 × 10(-8)), seven of which are new for these cancer sites. Oral and pharyngeal cancers combined were associated with loci at 6p21.32 (rs3828805, HLA-DQB1), 10q26.13 (rs201982221, LHPP) and 11p15.4 (rs1453414, OR52N2-TRIM5). Oral cancer was associated with two new regions, 2p23.3 (rs6547741, GPN1) and 9q34.12 (rs928674, LAMC3), and with known cancer-related loci-9p21.3 (rs8181047, CDKN2B-AS1) and 5p15.33 (rs10462706, CLPTM1L). Oropharyngeal cancer associations were limited to the human leukocyte antigen (HLA) region, and classical HLA allele imputation showed a protective association with the class II haplotype HLA-DRB1*1301-HLA-DQA1*0103-HLA-DQB1*0603 (odds ratio (OR) = 0.59, P = 2.7 × 10(-9)). Stratified analyses on a subgroup of oropharyngeal cases with information available on human papillomavirus (HPV) status indicated that this association was considerably stronger in HPV-positive (OR = 0.23, P = 1.6 × 10(-6)) than in HPV-negative (OR = 0.75, P = 0.16) cancers.en
dc.description.sponsorshipGenotyping performed at the Center for Inherited Disease Research (CIDR) was funded through the U.S. National Institute of Dental and Craniofacial Research (NIDCR) grant 1X01HG007780-0. Genotyping for shared controls with the Lung OncoArray initiative was funded through the grant X01HG007492-0. Corina Lesseur undertook this work during the tenure of a Postdoctoral Fellowship awarded by the International Agency for Research on Cancer. The funders did not participate in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. We acknowledge all of the participants involved in this research and the funders and support. We thank Dr. Leticia Fernandez (Instituto Nacional de Oncologia y Radiobiologia, La Habana, Cuba) for her contribution to the IARC ORC multicenter study. We are also grateful to Sergio Koifman (Escola Nacional de Saúde Pública, Rio de Janeiro, Brazil) for his contribution to the IARC Latin America multicenter study (Sergio Koifman passed away in May 2014) and to Xavier Castellsagué from the ARCAGE Barcelona Center who recently passed away (June 2016). The University of Pittsburgh head and neck cancer case-control study is supported by National Institutes of Health grants P50 CA097190 and P30 CA047904. The Carolina Head and Neck Cancer Study (CHANCE) was supported by the National Cancer Institute (R01-CA90731). The Head and Neck Genome Project (GENCAPO) was supported by the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) (Grant numbers 04/12054-9 and 10/51168-0). The authors thank all the members of the GENCAPO team. The HN5000 study was funded by the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research scheme (RP-PG-0707-10034), the views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. The Toronto study was funded by the Canadian Cancer Society Research Institute (020214) and the National Cancer Institute (U19 CA148127) and the Cancer Care Ontario Research Chair. The alcohol-related cancers and genetic susceptibility study in Europe (ARCAGE) was funded by the European Commission’s 5th Framework Program (QLK1-2001-00182), the Italian Association for Cancer Research, Compagnia di San Paolo/FIRMS, Region Piemonte, and Padova University (CPDA057222).The Rome Study was supported by the Associazione Italiana per la Ricerca sul Cancro (AIRC) IG 2011 10491 and IG2013 14220 to SB, and Fondazione Veronesi to SB. The IARC Latin American study was funded by the European Commission INCO-DC programme (IC18-CT97-0222), with additional funding from Fondo para la Investigacion Cientifica y Tecnologica (Argentina) and the Fundação de Amparo à Pesquisa do Estado de São Paulo (01/01768-2). The IARC Central Europe study was supported by European Commission’s INCO-COPERNICUS Program (IC15-CT98-0332), NIH/National Cancer Institute grant CA92039, and the World Cancer Research Foundation grant WCRF 99A28.The IARC Oral Cancer Multicenter study was funded by: grant S06 96 202489 05F02 from Europe against Cancer; Grants FIS 97/0024, FIS 97/0662, and BAE 01/5013 from Fondo de Investigaciones Sanitarias, Spain; UICC Yamagiwa-Yoshida Memorial International Cancer Study; National Cancer Institute of Canada; Italian Association for Research on Cancer; and the Pan American Health Organization. The coordination of EPIC study is financially supporteden
dc.language.isoenen
dc.relation.hasparthttp://ecnis.openrepository.com/ecnis/handle/10146/618165-
dc.relation.urlhttps://www.nature.com/ng/journal/v48/n12/full/ng.3685.htmlen
dc.rightsArchived with thanks to Nature geneticsen
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/*
dc.subjectepidemiologyen
dc.subjectgenetic researchen
dc.subjectGenome-Wide Association Studyen
dc.subjectoral canceren
dc.subject.meshAged-
dc.subject.meshCase-Control Studies-
dc.subject.meshFemale-
dc.subject.meshGenetic Markers-
dc.subject.meshGenetic Predisposition to Disease-
dc.subject.meshGenetic Variation-
dc.subject.meshGenome-Wide Association Study-
dc.subject.meshHLA Antigens-
dc.subject.meshHaplotypes-
dc.subject.meshHumans-
dc.subject.meshMale-
dc.subject.meshMiddle Aged-
dc.subject.meshMouth-
dc.subject.meshMouth Neoplasms-
dc.subject.meshPapillomaviridae-
dc.subject.meshPapillomavirus Infections-
dc.subject.meshPharyngeal Neoplasms-
dc.titleGenome-wide association analyses identify new susceptibility loci for oral cavity and pharyngeal cancer.en
dc.typeArticleen
dc.contributor.departmentNofer Institute of Occupational Medicine, Łódź, Polanden
dc.identifier.journalNature Geneticsen

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