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-Dabrowska; 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 RobinsonWolfgang Ahrens, Cristina Canova, Ariana Znaor, Xavier Castellsagué, David I. Conway, Ivana Holcátová, Dana Mates, Marta Vilensky, Claire M. Healy, Neonila Szeszenia-Dabrowska, 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 â'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
DOIs	https://doi.org/10.1038/ng.3685
State	Published - 1 Dec 2016

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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

@article{e6c416c7c3aa46d99d8587d3c6be9f91,

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 {\^a}'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.",

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-Dabrowska 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",

year = "2016",

month = dec,

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doi = "10.1038/ng.3685",

language = "English",

volume = "48",

pages = "1544--1550",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "12",

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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-Dabrowska, 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

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-Dabrowska, 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

PY - 2016/12/1

Y1 - 2016/12/1

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 â'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 â'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.

UR - http://www.scopus.com/inward/record.url?scp=84991660575&partnerID=8YFLogxK

U2 - 10.1038/ng.3685

DO - 10.1038/ng.3685

M3 - Article

C2 - 27749845

AN - SCOPUS:84991660575

VL - 48

SP - 1544

EP - 1550

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 12

ER -

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

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