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

Corina Lesseur, B. Diergaarde, Andrew F. Olshan, Victor Wünsch-Filho, Andrew R. Ness, Geoffrey Liu, Martin Lacko, Jose Eluf-Neto, Silvia Franceschi, Pagona Lagiou, Gary J. Macfarlane, Lorenzo Richiardi, Stefania Boccia, Jerry Polesel, Kristina Kjaerheim, David Zaridze, Mattias Johansson, Ana 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, Neonilia Szeszenia-Dabrowska, Eleonora Fabianova, Jolanta Lissowska, Jennifer R. Grandis, Mark C. Weissler, Eloiza H. Tajara, Fabio D. Nunes, Marcos Brasilino De Carvalho, Steve Thomas, Rayjean J. Hung, Wilbert H M Peters, Rolando Herrero, Gabriella Cadoni, H. B. Bueno-De-Mesquita, A. Steffen, Antonio Agudo, Oxana Shangina, Xiangjun Xiao, Valérie Gaborieau, Amelie Chabrier, Devasena Anantharaman, Paolo Boffetta, Christopher I. Amos, James McKay, Paul Brennan

Research output: Contribution to journalArticle

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
JournalNature Genetics
DOIs
Publication statusAccepted/In press - Oct 17 2016

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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

ASJC Scopus subject areas

  • Genetics

Cite this

Lesseur, C., Diergaarde, B., Olshan, A. F., Wünsch-Filho, V., Ness, A. R., Liu, G., ... Brennan, P. (Accepted/In press). Genome-wide association analyses identify new susceptibility loci for oral cavity and pharyngeal cancer. Nature Genetics. https://doi.org/10.1038/ng.3685

Genome-wide association analyses identify new susceptibility loci for oral cavity and pharyngeal cancer. / Lesseur, Corina; Diergaarde, B.; Olshan, Andrew F.; Wünsch-Filho, Victor; Ness, Andrew R.; Liu, Geoffrey; Lacko, Martin; Eluf-Neto, Jose; Franceschi, Silvia; Lagiou, Pagona; Macfarlane, Gary J.; Richiardi, Lorenzo; Boccia, Stefania; Polesel, Jerry; Kjaerheim, Kristina; Zaridze, David; Johansson, Mattias; Menezes, Ana; 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, Neonilia; Fabianova, Eleonora; Lissowska, Jolanta; Grandis, Jennifer R.; Weissler, Mark C.; Tajara, Eloiza H.; Nunes, Fabio D.; De Carvalho, Marcos Brasilino; Thomas, Steve; Hung, Rayjean J.; Peters, Wilbert H M; Herrero, Rolando; Cadoni, Gabriella; Bueno-De-Mesquita, H. B.; Steffen, A.; Agudo, Antonio; Shangina, Oxana; Xiao, Xiangjun; Gaborieau, Valérie; Chabrier, Amelie; Anantharaman, Devasena; Boffetta, Paolo; Amos, Christopher I.; McKay, James; Brennan, Paul.

In: Nature Genetics, 17.10.2016.

Research output: Contribution to journalArticle

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, A, Curado, MP, Robinson, M, Ahrens, W, Canova, C, Znaor, A, Castellsagué, X, Conway, DI, Holcátová, I, Mates, D, Vilensky, M, Healy, CM, Szeszenia-Dabrowska, N, Fabianova, 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, J & Brennan, P 2016, 'Genome-wide association analyses identify new susceptibility loci for oral cavity and pharyngeal cancer', Nature Genetics. https://doi.org/10.1038/ng.3685
Lesseur, Corina ; Diergaarde, B. ; Olshan, Andrew F. ; Wünsch-Filho, Victor ; Ness, Andrew R. ; Liu, Geoffrey ; Lacko, Martin ; Eluf-Neto, Jose ; Franceschi, Silvia ; Lagiou, Pagona ; Macfarlane, Gary J. ; Richiardi, Lorenzo ; Boccia, Stefania ; Polesel, Jerry ; Kjaerheim, Kristina ; Zaridze, David ; Johansson, Mattias ; Menezes, Ana ; 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, Neonilia ; Fabianova, Eleonora ; Lissowska, Jolanta ; Grandis, Jennifer R. ; Weissler, Mark C. ; Tajara, Eloiza H. ; Nunes, Fabio D. ; De Carvalho, Marcos Brasilino ; Thomas, Steve ; Hung, Rayjean J. ; Peters, Wilbert H M ; Herrero, Rolando ; Cadoni, Gabriella ; Bueno-De-Mesquita, H. B. ; Steffen, A. ; Agudo, Antonio ; Shangina, Oxana ; Xiao, Xiangjun ; Gaborieau, Valérie ; Chabrier, Amelie ; Anantharaman, Devasena ; Boffetta, Paolo ; Amos, Christopher I. ; McKay, James ; Brennan, Paul. / Genome-wide association analyses identify new susceptibility loci for oral cavity and pharyngeal cancer. In: Nature Genetics. 2016.
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AU - Wünsch-Filho, Victor

AU - Ness, Andrew R.

AU - Liu, Geoffrey

AU - Lacko, Martin

AU - Eluf-Neto, Jose

AU - Franceschi, Silvia

AU - Lagiou, Pagona

AU - Macfarlane, Gary J.

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AU - Lissowska, Jolanta

AU - Grandis, Jennifer R.

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AU - Xiao, Xiangjun

AU - Gaborieau, Valérie

AU - Chabrier, Amelie

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