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 & 34 others 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

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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 languageEnglish
Pages (from-to)1544-1550
Number of pages7
JournalNature Genetics
Volume48
Issue number12
Early online dateOct 2016
DOIs
Publication statusPublished - Dec 2016

Fingerprint

Pharyngeal Neoplasms
Genome-Wide Association Study
Mouth Neoplasms
HLA Antigens
Mouth
Odds Ratio
Oropharyngeal Neoplasms
Human papillomavirus 6
Neoplasms
South America
North America
Haplotypes
Alleles

Keywords

  • epidemiology
  • genetics research
  • genome-wide association studies
  • oral cancer

Cite this

Lesseur, C., Diergaarde, B., Olshan, A. F., Wünsch-Filho, V., Ness, A. R., Liu, G., ... 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

Genome-wide association analyses identify new susceptibility loci for oral cavity and pharyngeal cancer. / 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-Dąbrowska, Neonila; 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.

In: Nature Genetics, Vol. 48, No. 12, 12.2016, p. 1544-1550.

Research output: Contribution to journalLetter

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
Lesseur C, Diergaarde B, Olshan AF, Wünsch-Filho V, Ness AR, Liu G et al. Genome-wide association analyses identify new susceptibility loci for oral cavity and pharyngeal cancer. Nature Genetics. 2016 Dec;48(12):1544-1550. https://doi.org/10.1038/ng.3685
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-Dąbrowska, Neonila ; 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. / Genome-wide association analyses identify new susceptibility loci for oral cavity and pharyngeal cancer. In: Nature Genetics. 2016 ; Vol. 48, No. 12. pp. 1544-1550.
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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 × 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.",
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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–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{\cc}{\~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{\cc}{\~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 = "12",
doi = "10.1038/ng.3685",
language = "English",
volume = "48",
pages = "1544--1550",
journal = "Nature Genetics",
issn = "1061-4036",
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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

VL - 48

SP - 1544

EP - 1550

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 12

ER -