Genome-wide association meta-analysis identifies pleiotropic risk loci for aerodigestive squamous cell cancers

Corina Lesseur; Aida Ferreiro-Iglesias; James D. Mckay; Yohan Bossé; Mattias Johansson; Valerie Gaborieau; Maria Teresa Landi; David C. Christiani; Neil C. Caporaso; Stig E. Bojesen; Christopher I. Amos; Sanjay Shete; Geoffrey Liu; Guopeng Liu; Gadi Rennert; Demetrios Albanes; Melinda C. Aldrich; Adonina Tardon; Chu Chen; Chen Chen; Liloglou Triantafillos; John K. Field; Marion Dawn Teare; Lambertus A. Kiemeney; Brenda Diergaarde; Robert L. Ferris; Shanbeh Zienolddiny; Stephen Lam; Andrew F. Olshan; Mark C. Weissler; Martin Lacko; Angela Risch; Heike Bickeböller; Andy R. Ness; Steve Thomas; Loic Le Marchand; Matthew B. Schabath; Victor Wünsch-Filho; Eloiza H. Tajara; Angeline S. Andrew; Gary M. Clifford; Philip Lazarus; Kjell Grankvist; Mikael Johansson; Susanne Arnold; Olle Melander; Hans Brunnström; Stefania Boccia; Gabriella Cadoni; Wim Timens; Ma'En Obeidat; Xiangjun Xiao; Richard S. Houlston; Rayjean J. Hung; Paul Brennan

doi:10.1371/journal.pgen.1009254

Genome-wide association meta-analysis identifies pleiotropic risk loci for aerodigestive squamous cell cancers

Corina Lesseur, Aida Ferreiro-Iglesias, James D. Mckay, Yohan Bossé, Mattias Johansson, Valerie Gaborieau, Maria Teresa Landi, David C. Christiani, Neil C. Caporaso, Stig E. Bojesen, Christopher I. Amos, Sanjay Shete, Geoffrey Liu, Guopeng Liu, Gadi Rennert, Demetrios Albanes, Melinda C. Aldrich, Adonina Tardon, Chu Chen, Chen ChenLiloglou Triantafillos, John K. Field, Marion Dawn Teare, Lambertus A. Kiemeney, Brenda Diergaarde, Robert L. Ferris, Shanbeh Zienolddiny, Stephen Lam, Andrew F. Olshan, Mark C. Weissler, Martin Lacko, Angela Risch, Heike Bickeböller, Andy R. Ness, Steve Thomas, Loic Le Marchand, Matthew B. Schabath, Victor Wünsch-Filho, Eloiza H. Tajara, Angeline S. Andrew, Gary M. Clifford, Philip Lazarus, Kjell Grankvist, Mikael Johansson, Susanne Arnold, Olle Melander, Hans Brunnström, Stefania Boccia, Gabriella Cadoni, Wim Timens, Ma'En Obeidat, Xiangjun Xiao, Richard S. Houlston, Rayjean J. Hung, Paul Brennan

Risultato della ricerca: Contributo in rivista › Articolo in rivista

Abstract

Squamous cell carcinomas (SqCC) of the aerodigestive tract have similar etiological risk factors. Although genetic risk variants for individual cancers have been identified, an agnostic, genome-wide search for shared genetic susceptibility has not been performed. To identify novel and pleotropic SqCC risk variants, we performed a meta-analysis of GWAS data on lung SqCC (LuSqCC), oro/pharyngeal SqCC (OSqCC), laryngeal SqCC (LaSqCC) and esophageal SqCC (ESqCC) cancers, totaling 13,887 cases and 61,961 controls of European ancestry. We identified one novel genome-wide significant (Pmeta<5x10-8) aerodigestive SqCC susceptibility loci in the 2q33.1 region (rs56321285, TMEM273). Additionally, three previously unknown loci reached suggestive significance (Pmeta<5x10-7): 1q32.1 (rs12133735, near MDM4), 5q31.2 (rs13181561, TMEM173) and 19p13.11 (rs61494113, ABHD8). Multiple previously identified loci for aerodigestive SqCC also showed evidence of pleiotropy in at least another SqCC site, these include: 4q23 (ADH1B), 6p21.33 (STK19), 6p21.32 (HLA-DQB1), 9p21.33 (CDKN2B-AS1) and 13q13.1(BRCA2). Gene-based association and gene set enrichment identified a set of 48 SqCC-related genes to DNA damage and epigenetic regulation pathways. Our study highlights the importance of cross-cancer analyses to identify pleiotropic risk loci of histology-related cancers arising at distinct anatomical sites.

Lingua originale	English
pagine (da-a)	e1009254-e1009254
Rivista	PLoS Genetics
Volume	17
DOI	https://doi.org/10.1371/journal.pgen.1009254
Stato di pubblicazione	Pubblicato - 2021

Keywords

head and neck

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10.1371/journal.pgen.1009254

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Lesseur, C., Ferreiro-Iglesias, A., Mckay, J. D., Bossé, Y., Johansson, M., Gaborieau, V., Landi, M. T., Christiani, D. C., Caporaso, N. C., Bojesen, S. E., Amos, C. I., Shete, S., Liu, G., Liu, G., Rennert, G., Albanes, D., Aldrich, M. C., Tardon, A., Chen, C., ... Brennan, P. (2021). Genome-wide association meta-analysis identifies pleiotropic risk loci for aerodigestive squamous cell cancers. PLoS Genetics, 17, e1009254-e1009254. https://doi.org/10.1371/journal.pgen.1009254

@article{8137d3ec8a764064aa768abe83119c24,

title = "Genome-wide association meta-analysis identifies pleiotropic risk loci for aerodigestive squamous cell cancers",

abstract = "Squamous cell carcinomas (SqCC) of the aerodigestive tract have similar etiological risk factors. Although genetic risk variants for individual cancers have been identified, an agnostic, genome-wide search for shared genetic susceptibility has not been performed. To identify novel and pleotropic SqCC risk variants, we performed a meta-analysis of GWAS data on lung SqCC (LuSqCC), oro/pharyngeal SqCC (OSqCC), laryngeal SqCC (LaSqCC) and esophageal SqCC (ESqCC) cancers, totaling 13,887 cases and 61,961 controls of European ancestry. We identified one novel genome-wide significant (Pmeta<5x10-8) aerodigestive SqCC susceptibility loci in the 2q33.1 region (rs56321285, TMEM273). Additionally, three previously unknown loci reached suggestive significance (Pmeta<5x10-7): 1q32.1 (rs12133735, near MDM4), 5q31.2 (rs13181561, TMEM173) and 19p13.11 (rs61494113, ABHD8). Multiple previously identified loci for aerodigestive SqCC also showed evidence of pleiotropy in at least another SqCC site, these include: 4q23 (ADH1B), 6p21.33 (STK19), 6p21.32 (HLA-DQB1), 9p21.33 (CDKN2B-AS1) and 13q13.1(BRCA2). Gene-based association and gene set enrichment identified a set of 48 SqCC-related genes to DNA damage and epigenetic regulation pathways. Our study highlights the importance of cross-cancer analyses to identify pleiotropic risk loci of histology-related cancers arising at distinct anatomical sites.",

keywords = "head and neck, head and neck",

author = "Corina Lesseur and Aida Ferreiro-Iglesias and Mckay, {James D.} and Yohan Boss{\'e} and Mattias Johansson and Valerie Gaborieau and Landi, {Maria Teresa} and Christiani, {David C.} and Caporaso, {Neil C.} and Bojesen, {Stig E.} and Amos, {Christopher I.} and Sanjay Shete and Geoffrey Liu and Guopeng Liu and Gadi Rennert and Demetrios Albanes and Aldrich, {Melinda C.} and Adonina Tardon and Chu Chen and Chen Chen and Liloglou Triantafillos and Field, {John K.} and Teare, {Marion Dawn} and Kiemeney, {Lambertus A.} and Brenda Diergaarde and Ferris, {Robert L.} and Shanbeh Zienolddiny and Stephen Lam and Olshan, {Andrew F.} and Weissler, {Mark C.} and Martin Lacko and Angela Risch and Heike Bickeb{\"o}ller and Ness, {Andy R.} and Steve Thomas and {Le Marchand}, Loic and Schabath, {Matthew B.} and Victor W{\"u}nsch-Filho and Tajara, {Eloiza H.} and Andrew, {Angeline S.} and Clifford, {Gary M.} and Philip Lazarus and Kjell Grankvist and Mikael Johansson and Susanne Arnold and Olle Melander and Hans Brunnstr{\"o}m and Stefania Boccia and Gabriella Cadoni and Wim Timens and Ma'En Obeidat and Xiangjun Xiao and Houlston, {Richard S.} and Hung, {Rayjean J.} and Paul Brennan",

year = "2021",

doi = "10.1371/journal.pgen.1009254",

language = "English",

volume = "17",

pages = "e1009254--e1009254",

journal = "PLoS Genetics",

issn = "1553-7390",

publisher = "San Francisco, CA : Public Library of Science, c2005-",

}

Lesseur, C, Ferreiro-Iglesias, A, Mckay, JD, Bossé, Y, Johansson, M, Gaborieau, V, Landi, MT, Christiani, DC, Caporaso, NC, Bojesen, SE, Amos, CI, Shete, S, Liu, G, Liu, G, Rennert, G, Albanes, D, Aldrich, MC, Tardon, A, Chen, C, Chen, C, Triantafillos, L, Field, JK, Teare, MD, Kiemeney, LA, Diergaarde, B, Ferris, RL, Zienolddiny, S, Lam, S, Olshan, AF, Weissler, MC, Lacko, M, Risch, A, Bickeböller, H, Ness, AR, Thomas, S, Le Marchand, L, Schabath, MB, Wünsch-Filho, V, Tajara, EH, Andrew, AS, Clifford, GM, Lazarus, P, Grankvist, K, Johansson, M, Arnold, S, Melander, O, Brunnström, H, Boccia, S , Cadoni, G, Timens, W, Obeidat, ME, Xiao, X, Houlston, RS, Hung, RJ & Brennan, P 2021, 'Genome-wide association meta-analysis identifies pleiotropic risk loci for aerodigestive squamous cell cancers', PLoS Genetics, vol. 17, pagg. e1009254-e1009254. https://doi.org/10.1371/journal.pgen.1009254

TY - JOUR

T1 - Genome-wide association meta-analysis identifies pleiotropic risk loci for aerodigestive squamous cell cancers

AU - Lesseur, Corina

AU - Ferreiro-Iglesias, Aida

AU - Mckay, James D.

AU - Bossé, Yohan

AU - Johansson, Mattias

AU - Gaborieau, Valerie

AU - Landi, Maria Teresa

AU - Christiani, David C.

AU - Caporaso, Neil C.

AU - Bojesen, Stig E.

AU - Amos, Christopher I.

AU - Shete, Sanjay

AU - Liu, Geoffrey

AU - Liu, Guopeng

AU - Rennert, Gadi

AU - Albanes, Demetrios

AU - Aldrich, Melinda C.

AU - Tardon, Adonina

AU - Chen, Chu

AU - Chen, Chen

AU - Triantafillos, Liloglou

AU - Field, John K.

AU - Teare, Marion Dawn

AU - Kiemeney, Lambertus A.

AU - Diergaarde, Brenda

AU - Ferris, Robert L.

AU - Zienolddiny, Shanbeh

AU - Lam, Stephen

AU - Olshan, Andrew F.

AU - Weissler, Mark C.

AU - Lacko, Martin

AU - Risch, Angela

AU - Bickeböller, Heike

AU - Ness, Andy R.

AU - Thomas, Steve

AU - Le Marchand, Loic

AU - Schabath, Matthew B.

AU - Wünsch-Filho, Victor

AU - Tajara, Eloiza H.

AU - Andrew, Angeline S.

AU - Clifford, Gary M.

AU - Lazarus, Philip

AU - Grankvist, Kjell

AU - Johansson, Mikael

AU - Arnold, Susanne

AU - Melander, Olle

AU - Brunnström, Hans

AU - Boccia, Stefania

AU - Cadoni, Gabriella

AU - Timens, Wim

AU - Obeidat, Ma'En

AU - Xiao, Xiangjun

AU - Houlston, Richard S.

AU - Hung, Rayjean J.

AU - Brennan, Paul

PY - 2021

Y1 - 2021

N2 - Squamous cell carcinomas (SqCC) of the aerodigestive tract have similar etiological risk factors. Although genetic risk variants for individual cancers have been identified, an agnostic, genome-wide search for shared genetic susceptibility has not been performed. To identify novel and pleotropic SqCC risk variants, we performed a meta-analysis of GWAS data on lung SqCC (LuSqCC), oro/pharyngeal SqCC (OSqCC), laryngeal SqCC (LaSqCC) and esophageal SqCC (ESqCC) cancers, totaling 13,887 cases and 61,961 controls of European ancestry. We identified one novel genome-wide significant (Pmeta<5x10-8) aerodigestive SqCC susceptibility loci in the 2q33.1 region (rs56321285, TMEM273). Additionally, three previously unknown loci reached suggestive significance (Pmeta<5x10-7): 1q32.1 (rs12133735, near MDM4), 5q31.2 (rs13181561, TMEM173) and 19p13.11 (rs61494113, ABHD8). Multiple previously identified loci for aerodigestive SqCC also showed evidence of pleiotropy in at least another SqCC site, these include: 4q23 (ADH1B), 6p21.33 (STK19), 6p21.32 (HLA-DQB1), 9p21.33 (CDKN2B-AS1) and 13q13.1(BRCA2). Gene-based association and gene set enrichment identified a set of 48 SqCC-related genes to DNA damage and epigenetic regulation pathways. Our study highlights the importance of cross-cancer analyses to identify pleiotropic risk loci of histology-related cancers arising at distinct anatomical sites.

AB - Squamous cell carcinomas (SqCC) of the aerodigestive tract have similar etiological risk factors. Although genetic risk variants for individual cancers have been identified, an agnostic, genome-wide search for shared genetic susceptibility has not been performed. To identify novel and pleotropic SqCC risk variants, we performed a meta-analysis of GWAS data on lung SqCC (LuSqCC), oro/pharyngeal SqCC (OSqCC), laryngeal SqCC (LaSqCC) and esophageal SqCC (ESqCC) cancers, totaling 13,887 cases and 61,961 controls of European ancestry. We identified one novel genome-wide significant (Pmeta<5x10-8) aerodigestive SqCC susceptibility loci in the 2q33.1 region (rs56321285, TMEM273). Additionally, three previously unknown loci reached suggestive significance (Pmeta<5x10-7): 1q32.1 (rs12133735, near MDM4), 5q31.2 (rs13181561, TMEM173) and 19p13.11 (rs61494113, ABHD8). Multiple previously identified loci for aerodigestive SqCC also showed evidence of pleiotropy in at least another SqCC site, these include: 4q23 (ADH1B), 6p21.33 (STK19), 6p21.32 (HLA-DQB1), 9p21.33 (CDKN2B-AS1) and 13q13.1(BRCA2). Gene-based association and gene set enrichment identified a set of 48 SqCC-related genes to DNA damage and epigenetic regulation pathways. Our study highlights the importance of cross-cancer analyses to identify pleiotropic risk loci of histology-related cancers arising at distinct anatomical sites.

KW - head and neck

UR - http://hdl.handle.net/10807/175363

U2 - 10.1371/journal.pgen.1009254

DO - 10.1371/journal.pgen.1009254

M3 - Article

SN - 1553-7390

VL - 17

SP - e1009254-e1009254

JO - PLoS Genetics

JF - PLoS Genetics

ER -

Genome-wide association meta-analysis identifies pleiotropic risk loci for aerodigestive squamous cell cancers

Abstract

Keywords

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