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

Corina Lesseur; Brenda Diergaarde; Andrew F Olshan; Victor Wünsch-Filho; Andrew R Ness; Geoffrey Liu; Martin Lacko; José Eluf-Neto; Silvia Franceschi; Pagona Lagiou; Gary J Macfarlane; Lorenzo Richiardi; Stefania Boccia; Jerry Polesel; Kristina Kjaerheim; David Zaridze; Mattias Johansson; Ana M Menezes; Maria Paula Curado; Max Robinson; Wolfgang Ahrens; Cristina Canova; Ariana Znaor; Xavier Castellsagué; David I Conway; Ivana Holcátová; Dana Mates; Marta Vilensky; Claire M Healy; Neonila Szeszenia-Dąbrowska; Eleonóra Fabiánová; Jolanta Lissowska; Jennifer R Grandis; Mark C Weissler; Eloiza H Tajara; Fabio D Nunes; Marcos B de Carvalho; Steve Thomas; Rayjean J Hung; Wilbert H M Peters; Rolando Herrero; Gabriella Cadoni; H Bas Bueno-de-Mesquita; Annika Steffen; Antonio Agudo; Oxana Shangina; Xiangjun Xiao; Valérie Gaborieau; Amélie Chabrier; Devasena Anantharaman; Paolo Boffetta; Christopher I Amos; James D McKay; Paul Brennan

doi:10.1038/ng.3685

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

Corina Lesseur
, Brenda Diergaarde
, Andrew F Olshan
, Victor Wünsch-Filho
, Andrew R Ness
, Geoffrey Liu
, Martin Lacko
, José Eluf-Neto
, Silvia Franceschi
, Pagona Lagiou
, Gary J Macfarlane
, Lorenzo Richiardi
, Stefania Boccia
, Jerry Polesel
, Kristina Kjaerheim
, David Zaridze
, Mattias Johansson
, Ana M Menezes
, Maria Paula Curado
, Max Robinson

Wolfgang Ahrens, Cristina Canova, Ariana Znaor, Xavier Castellsagué, David I Conway, Ivana Holcátová, Dana Mates, Marta Vilensky, Claire M Healy, Neonila Szeszenia-Dąbrowska, Eleonóra Fabiánová, Jolanta Lissowska, Jennifer R Grandis, Mark C Weissler, Eloiza H Tajara, Fabio D Nunes, Marcos B de Carvalho, Steve Thomas, Rayjean J Hung, Wilbert H M Peters, Rolando Herrero, Gabriella Cadoni, H Bas Bueno-de-Mesquita, Annika Steffen, Antonio Agudo, Oxana Shangina, Xiangjun Xiao, Valérie Gaborieau, Amélie Chabrier, Devasena Anantharaman, Paolo Boffetta, Christopher I Amos, James D McKay, Paul Brennan

International Agency for Research on Cancer
University of Pittsburgh
University of North Carolina at Chapel Hill
UNIVERSIDADE DE SAO PAULO, BRAZIL
University Hospitals Bristol NHS Foundation Trust
Princess Margaret Cancer Centre, Toronto, Ontario, Canada.
Maastricht University
University of Turin
Section of Hygiene, Institute of Public Health, Università Cattolica del Sacro Cuore, Fondazione Policlinico 'Agostino Gemelli', Rome, Italy.
Unit of Cancer Epidemiology, CRO Aviano National Cancer Institute, Aviano, Italy.
Cancer Registry of Norway, Oslo, Norway.
N.N. Blokhin Russian Cancer Research Centre of the Russian Ministry of Health, Moscow
Programa de Pós-Graduacão em Epidemiologia, Universidade Federal de Pelotas (UFPel), Pelotas, Brazil.
Epidemiology, International Center for Research (CIPE), A.C. Camargo Cancer Center, Sao Paulo, Brazil.
Newcastle University
Leibniz Institute for Prevention Research and Epidemiology - BIPS, Bremen, Germany.
Universita di Padova
Institut Català d'Oncologia (ICO)-IDIBELL, CIBERESP, l'Hospitalet de Llobregat, Barcelona, Spain.
University of Glasgow
Charles University
National Institute of Public Health
Universidad de Buenos Aires, Buenos Aires, Argentina.
Trinity College Dublin
Department of Environmental Epidemiology, Nofer Institute of Occupational Medicine, Lodz, Poland.
Regional Authority of Public Health
Maria Skłodowska-Curie Memorial Cancer Centre and Institute of Oncology (MCMCC), Warsaw, Poland.
University of California at San Francisco
Department of Molecular Biology, School of Medicine of São José do Rio Preto, São José do Rio Preto, Brazil.
Department of Head and Neck Surgery, Heliópolis Hospital, São Paulo, Brazil.
University of Bristol
Lunenfeld-Tanenbaum Research Institute
Radboud University Medical Center
Institute of Otorhinolaryngology, Università Cattolica del Sacro Cuore, Fondazione Policlinico 'Agostino Gemelli', Rome, Italy.
National Institute for Public Health and the Environment (RIVM)
German Institute of Human Nutrition in Potsdam-Rehbruecke (DIfE), Nuthetal, Germany.
Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Institut Català d'Oncologia (ICO)-IDIBELL, l'Hospitalet de Llobregat, Barcelona, Spain.
Geisel School of Medicine at Dartmouth
Icahn School of Medicine at Mount Sinai
National and Kapodistrian University of Athens

Research output: Contribution to journal › Letter › peer-review

195 Citations (Scopus)

29 Downloads (Pure)

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.

Original language	English
Pages (from-to)	1544-1550
Number of pages	7
Journal	Nature Genetics
Volume	48
Issue number	12
Early online date	Oct 2016
DOIs	https://doi.org/10.1038/ng.3685
Publication status	Published - Dec 2016

Bibliographical note

Genotyping performed at the Center for Inherited Disease Research (CIDR) was funded through US National Institute of Dental and Craniofacial Research (NIDCR) grant 1X01HG007780-0. Genotyping for shared controls with the Lung OncoArray initiative was funded through grant X01HG007492-0. C.L. 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 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 L. Fernandez for her contribution to the IARC ORC multicenter study. We are also grateful to S. Koifman for his contribution to the IARC Latin America multicenter study (S. Koifman passed away in May 2014) and to X. Castellsagué who recently passed away (June 2016).

The University of Pittsburgh head and neck cancer case–control study is supported by US National Institutes of Health grants P50CA097190 and P30CA047904. The Carolina Head and Neck Cancer Study (CHANCE) was supported by the National Cancer Institute (R01CA90731). The Head and Neck Genome Project (GENCAPO) was supported by the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP; grants 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 UK Department of Health. The Toronto study was funded by the Canadian Cancer Society Research Institute (020214) and the National Cancer Institute (U19CA148127) and by the Cancer Care Ontario Research Chair. The Alcohol-Related Cancers and Genetic Susceptibility Study in Europe (ARCAGE) was funded by the European Commission's fifth framework programme (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) awards IG 2011 10491 and IG 2013 14220 to S.B. and by Fondazione Veronesi to S.B. The IARC Latin American study was funded by the European Commission INCO-DC programme (IC18-CT97-0222), with additional funding from Fondo para la Investigación Científica y Tecnológica (Argentina) and the Fundação de Amparo à Pesquisa do Estado de São Paulo (01/01768-2). The IARC Central Europe study was supported by the European Commission's INCO-COPERNICUS Program (IC15-CT98-0332), US NIH/National Cancer Institute grant CA92039 and 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; the UICC Yamagiwa-Yoshida Memorial International Cancer Study; the National Cancer Institute of Canada; Associazione Italiana per la Ricerca sul Cancro; and the Pan-American Health Organization. Coordination of the EPIC study is financially supported by the European Commission (DG SANCO) and the International Agency for Research on Cancer.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

epidemiology
genetics research
genome-wide association studies
oral cancer

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Cite this

Lesseur, C., Diergaarde, B., Olshan, A. F., Wünsch-Filho, V., Ness, A. R., Liu, G., Lacko, M., Eluf-Neto, J., Franceschi, S., Lagiou, P., Macfarlane, G. J., Richiardi, L., Boccia, S., Polesel, J., Kjaerheim, K., Zaridze, D., Johansson, M., Menezes, A. M., Curado, M. P., ... Brennan, P. (2016). Genome-wide association analyses identify new susceptibility loci for oral cavity and pharyngeal cancer. Nature Genetics, 48(12), 1544-1550. https://doi.org/10.1038/ng.3685

Lesseur, C, Diergaarde, B, Olshan, AF, Wünsch-Filho, V, Ness, AR, Liu, G, Lacko, M, Eluf-Neto, J, Franceschi, S, Lagiou, P, Macfarlane, GJ, Richiardi, L, Boccia, S, Polesel, J, Kjaerheim, K, Zaridze, D, Johansson, M, Menezes, AM, Curado, MP, Robinson, M, Ahrens, W, Canova, C, Znaor, A, Castellsagué, X, Conway, DI, Holcátová, I, Mates, D, Vilensky, M, Healy, CM, Szeszenia-Dąbrowska, N, Fabiánová, E, Lissowska, J, Grandis, JR, Weissler, MC, Tajara, EH, Nunes, FD, de Carvalho, MB, Thomas, S, Hung, RJ, Peters, WHM, Herrero, R, Cadoni, G, Bueno-de-Mesquita, HB, Steffen, A, Agudo, A, Shangina, O, Xiao, X, Gaborieau, V, Chabrier, A, Anantharaman, D, Boffetta, P, Amos, CI, McKay, JD & Brennan, P 2016, 'Genome-wide association analyses identify new susceptibility loci for oral cavity and pharyngeal cancer', Nature Genetics, vol. 48, no. 12, pp. 1544-1550. https://doi.org/10.1038/ng.3685

@article{d132c75710fc4ba29904a881a8812ebc,

title = "Genome-wide association analyses identify new susceptibility loci for oral cavity and pharyngeal cancer",

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 {\texttimes} 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 {\texttimes} 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 {\texttimes} 10(-6)) than in HPV-negative (OR = 0.75, P = 0.16) cancers.",

keywords = "epidemiology, genetics research, genome-wide association studies, oral cancer",

author = "Corina Lesseur and Brenda Diergaarde and Olshan, \{Andrew F\} and Victor W{\"u}nsch-Filho and Ness, \{Andrew R\} and Geoffrey Liu and Martin Lacko and Jos{\'e} Eluf-Neto and Silvia Franceschi and Pagona Lagiou and Macfarlane, \{Gary J\} and Lorenzo Richiardi and Stefania Boccia and Jerry Polesel and Kristina Kjaerheim and David Zaridze and Mattias Johansson and Menezes, \{Ana M\} and Curado, \{Maria Paula\} and Max Robinson and Wolfgang Ahrens and Cristina Canova and Ariana Znaor and Xavier Castellsagu{\'e} and Conway, \{David I\} and Ivana Holc{\'a}tov{\'a} and Dana Mates and Marta Vilensky and Healy, \{Claire M\} and Neonila Szeszenia-D{\c a}browska and Eleon{\'o}ra Fabi{\'a}nov{\'a} and Jolanta Lissowska and Grandis, \{Jennifer R\} and Weissler, \{Mark C\} and Tajara, \{Eloiza H\} and Nunes, \{Fabio D\} and \{de Carvalho\}, \{Marcos B\} and Steve Thomas and Hung, \{Rayjean J\} and Peters, \{Wilbert H M\} and Rolando Herrero and Gabriella Cadoni and Bueno-de-Mesquita, \{H Bas\} and Annika Steffen and Antonio Agudo and Oxana Shangina and Xiangjun Xiao and Val{\'e}rie Gaborieau and Am{\'e}lie Chabrier and Devasena Anantharaman and Paolo Boffetta and Amos, \{Christopher I\} and McKay, \{James D\} and Paul Brennan",

note = "Genotyping performed at the Center for Inherited Disease Research (CIDR) was funded through US National Institute of Dental and Craniofacial Research (NIDCR) grant 1X01HG007780-0. Genotyping for shared controls with the Lung OncoArray initiative was funded through grant X01HG007492-0. C.L. 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 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 L. Fernandez for her contribution to the IARC ORC multicenter study. We are also grateful to S. Koifman for his contribution to the IARC Latin America multicenter study (S. Koifman passed away in May 2014) and to X. Castellsagu{\'e} who recently passed away (June 2016). The University of Pittsburgh head and neck cancer case{\textendash}control study is supported by US National Institutes of Health grants P50CA097190 and P30CA047904. The Carolina Head and Neck Cancer Study (CHANCE) was supported by the National Cancer Institute (R01CA90731). The Head and Neck Genome Project (GENCAPO) was supported by the Funda{\c c}{\~a}o de Amparo {\`a} Pesquisa do Estado de S{\~a}o Paulo (FAPESP; grants 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 UK Department of Health. The Toronto study was funded by the Canadian Cancer Society Research Institute (020214) and the National Cancer Institute (U19CA148127) and by the Cancer Care Ontario Research Chair. The Alcohol-Related Cancers and Genetic Susceptibility Study in Europe (ARCAGE) was funded by the European Commission's fifth framework programme (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) awards IG 2011 10491 and IG 2013 14220 to S.B. and by Fondazione Veronesi to S.B. The IARC Latin American study was funded by the European Commission INCO-DC programme (IC18-CT97-0222), with additional funding from Fondo para la Investigaci{\'o}n Cient{\'i}fica y Tecnol{\'o}gica (Argentina) and the Funda{\c c}{\~a}o de Amparo {\`a} Pesquisa do Estado de S{\~a}o Paulo (01/01768-2). The IARC Central Europe study was supported by the European Commission's INCO-COPERNICUS Program (IC15-CT98-0332), US NIH/National Cancer Institute grant CA92039 and 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; the UICC Yamagiwa-Yoshida Memorial International Cancer Study; the National Cancer Institute of Canada; Associazione Italiana per la Ricerca sul Cancro; and the Pan-American Health Organization. Coordination of the EPIC study is financially supported by the European Commission (DG SANCO) and the International Agency for Research on Cancer.",

year = "2016",

month = dec,

doi = "10.1038/ng.3685",

language = "English",

volume = "48",

pages = "1544--1550",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "12",

}

TY - JOUR

T1 - Genome-wide association analyses identify new susceptibility loci for oral cavity and pharyngeal cancer

AU - Lesseur, Corina

AU - Diergaarde, Brenda

AU - Olshan, Andrew F

AU - Wünsch-Filho, Victor

AU - Ness, Andrew R

AU - Liu, Geoffrey

AU - Lacko, Martin

AU - Eluf-Neto, José

AU - Franceschi, Silvia

AU - Lagiou, Pagona

AU - Macfarlane, Gary J

AU - Richiardi, Lorenzo

AU - Boccia, Stefania

AU - Polesel, Jerry

AU - Kjaerheim, Kristina

AU - Zaridze, David

AU - Johansson, Mattias

AU - Menezes, Ana M

AU - Curado, Maria Paula

AU - Robinson, Max

AU - Ahrens, Wolfgang

AU - Canova, Cristina

AU - Znaor, Ariana

AU - Castellsagué, Xavier

AU - Conway, David I

AU - Holcátová, Ivana

AU - Mates, Dana

AU - Vilensky, Marta

AU - Healy, Claire M

AU - Szeszenia-Dąbrowska, Neonila

AU - Fabiánová, Eleonóra

AU - Lissowska, Jolanta

AU - Grandis, Jennifer R

AU - Weissler, Mark C

AU - Tajara, Eloiza H

AU - Nunes, Fabio D

AU - de Carvalho, Marcos B

AU - Thomas, Steve

AU - Hung, Rayjean J

AU - Peters, Wilbert H M

AU - Herrero, Rolando

AU - Cadoni, Gabriella

AU - Bueno-de-Mesquita, H Bas

AU - Steffen, Annika

AU - Agudo, Antonio

AU - Shangina, Oxana

AU - Xiao, Xiangjun

AU - Gaborieau, Valérie

AU - Chabrier, Amélie

AU - Anantharaman, Devasena

AU - Boffetta, Paolo

AU - Amos, Christopher I

AU - McKay, James D

AU - Brennan, Paul

N1 - Genotyping performed at the Center for Inherited Disease Research (CIDR) was funded through US National Institute of Dental and Craniofacial Research (NIDCR) grant 1X01HG007780-0. Genotyping for shared controls with the Lung OncoArray initiative was funded through grant X01HG007492-0. C.L. 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 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 L. Fernandez for her contribution to the IARC ORC multicenter study. We are also grateful to S. Koifman for his contribution to the IARC Latin America multicenter study (S. Koifman passed away in May 2014) and to X. Castellsagué who recently passed away (June 2016). The University of Pittsburgh head and neck cancer case–control study is supported by US National Institutes of Health grants P50CA097190 and P30CA047904. The Carolina Head and Neck Cancer Study (CHANCE) was supported by the National Cancer Institute (R01CA90731). The Head and Neck Genome Project (GENCAPO) was supported by the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP; grants 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 UK Department of Health. The Toronto study was funded by the Canadian Cancer Society Research Institute (020214) and the National Cancer Institute (U19CA148127) and by the Cancer Care Ontario Research Chair. The Alcohol-Related Cancers and Genetic Susceptibility Study in Europe (ARCAGE) was funded by the European Commission's fifth framework programme (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) awards IG 2011 10491 and IG 2013 14220 to S.B. and by Fondazione Veronesi to S.B. The IARC Latin American study was funded by the European Commission INCO-DC programme (IC18-CT97-0222), with additional funding from Fondo para la Investigación Científica y Tecnológica (Argentina) and the Fundação de Amparo à Pesquisa do Estado de São Paulo (01/01768-2). The IARC Central Europe study was supported by the European Commission's INCO-COPERNICUS Program (IC15-CT98-0332), US NIH/National Cancer Institute grant CA92039 and 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; the UICC Yamagiwa-Yoshida Memorial International Cancer Study; the National Cancer Institute of Canada; Associazione Italiana per la Ricerca sul Cancro; and the Pan-American Health Organization. Coordination of the EPIC study is financially supported by the European Commission (DG SANCO) and the International Agency for Research on Cancer.

PY - 2016/12

Y1 - 2016/12

N2 - 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.

AB - 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.

KW - epidemiology

KW - genetics research

KW - genome-wide association studies

KW - oral cancer

U2 - 10.1038/ng.3685

DO - 10.1038/ng.3685

M3 - Letter

C2 - 27749845

SN - 1061-4036

VL - 48

SP - 1544

EP - 1550

JO - Nature Genetics

JF - Nature Genetics

IS - 12

ER -

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

Abstract

Bibliographical note

UN SDGs

Keywords

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