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

C. Lesseur; A. Ferreiro-Iglesias; J. D. McKay; Y. Bosse; M. Johansson; V. Gaborieau; M. T. Landi; D. C. Christiani; N. C. Caporaso; S. E. Bojesen; C. I. Amos; S. Shete; G. Liu; G. Rennert; D. Albanes; M. C. Aldrich; A. Tardon; C. Chen; L. Triantafillos; J. K. Field; M. D. Teare; L. A. Kiemeney; B. Diergaarde; R. L. Ferris; S. Zienolddiny; S. Lam; A. F. Olshan; M. C. Weissler; M. Lacko; A. Risch; H. Bickeboller; A. R. Ness; S. Thomas; Marchand L. Le; M. B. Schabath; V. Wunsch-Filho; E. H. Tajara; A. S. Andrew; G. M. Clifford; P. Lazarus; K. Grankvist; M. Johansson; S. Arnold; O. Melander; H. Brunnstrom; Stefania Boccia; Gabriella Cadoni; W. Timens; M. Obeidat; X. Xiao; R. S. Houlston; R. J. Hung; P. Brennan

doi:10.1371/journal.pgen.1009254

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

C. Lesseur
, A. Ferreiro-Iglesias
, J. D. McKay
, Y. Bosse
, M. Johansson
, V. Gaborieau
, M. T. Landi
, D. C. Christiani
, N. C. Caporaso
, S. E. Bojesen
, C. I. Amos
, S. Shete
, G. Liu
, G. Rennert
, D. Albanes
, M. C. Aldrich
, A. Tardon
, C. Chen
, L. Triantafillos
, J. K. Field

M. D. Teare, L. A. Kiemeney, B. Diergaarde, R. L. Ferris, S. Zienolddiny, S. Lam, A. F. Olshan, M. C. Weissler, M. Lacko, A. Risch, H. Bickeboller, A. R. Ness, S. Thomas, Marchand L. Le, M. B. Schabath, V. Wunsch-Filho, E. H. Tajara, A. S. Andrew, G. M. Clifford, P. Lazarus, K. Grankvist, M. Johansson, S. Arnold, O. Melander, H. Brunnstrom, Stefania Boccia, Gabriella Cadoni, W. Timens, M. Obeidat, X. Xiao, R. S. Houlston, R. J. Hung^*, P. Brennan^*

^*Corresponding author

International Agency for Research on Cancer
Icahn School of Medicine at Mount Sinai
University of Texas MD Anderson Cancer Center
Samuel Lunenfeld Research Institute of the Mount Sinai Hospital
Clalit Health Services
National Institutes of Health
University of Oviedo
University of Washington
University of Liverpool
University of Pittsburgh
Statens arbeidsmiljøinstitutt
Genome Sciences Centre
Maastricht University
University of Salzburg
German Cancer Research Center
University of Bristol
University of Hawai'i at Mānoa
Washington State University Spokane
Umeå University
University of Kentucky
Lund University
University of Groningen
University of British Columbia
Baylor College of Medicine

Research output: Contribution to journal › Article

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.

Original language	English
Pages (from-to)	e1009254-e1009254
Journal	PLoS Genetics
Volume	17
Issue number	3
DOIs	https://doi.org/10.1371/journal.pgen.1009254
Publication status	Published - 2021

UN SDGs

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

SDG 3 Good Health and Well-being

All Science Journal Classification (ASJC) codes

Ecology, Evolution, Behavior and Systematics
Molecular Biology
Genetics
Genetics(clinical)
Cancer Research

Keywords

head and neck

Access to Document

10.1371/journal.pgen.1009254

Cite this

Lesseur, C., Ferreiro-Iglesias, A., McKay, J. D., Bosse, Y., Johansson, M., Gaborieau, V., Landi, M. T., Christiani, D. C., Caporaso, N. C., Bojesen, S. E., Amos, C. I., Shete, S., Liu, G., Rennert, G., Albanes, D., Aldrich, M. C., Tardon, A., Chen, C., Triantafillos, L., ... Brennan, P. (2021). Genome-wide association meta-analysis identifies pleiotropic risk loci for aerodigestive squamous cell cancers. PLoS Genetics, 17(3), 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 = "C. Lesseur and A. Ferreiro-Iglesias and McKay, \{J. D.\} and Y. Bosse and M. Johansson and V. Gaborieau and Landi, \{M. T.\} and Christiani, \{D. C.\} and Caporaso, \{N. C.\} and Bojesen, \{S. E.\} and Amos, \{C. I.\} and S. Shete and G. Liu and G. Rennert and D. Albanes and Aldrich, \{M. C.\} and A. Tardon and C. Chen and L. Triantafillos and Field, \{J. K.\} and Teare, \{M. D.\} and Kiemeney, \{L. A.\} and B. Diergaarde and Ferris, \{R. L.\} and S. Zienolddiny and S. Lam and Olshan, \{A. F.\} and Weissler, \{M. C.\} and M. Lacko and A. Risch and H. Bickeboller and Ness, \{A. R.\} and S. Thomas and Le, \{Marchand L.\} and Schabath, \{M. B.\} and V. Wunsch-Filho and Tajara, \{E. H.\} and Andrew, \{A. S.\} and Clifford, \{G. M.\} and P. Lazarus and K. Grankvist and M. Johansson and S. Arnold and O. Melander and H. Brunnstrom and Stefania Boccia and Gabriella Cadoni and W. Timens and M. Obeidat and X. Xiao and Houlston, \{R. S.\} and Hung, \{R. J.\} and P. Brennan",

year = "2021",

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

language = "English",

volume = "17",

pages = "e1009254--e1009254",

journal = "PLoS Genetics",

issn = "1553-7390",

publisher = "Public Library of Science",

number = "3",

}

Lesseur, C, Ferreiro-Iglesias, A, McKay, JD, Bosse, Y, Johansson, M, Gaborieau, V, Landi, MT, Christiani, DC, Caporaso, NC, Bojesen, SE, Amos, CI, Shete, S, Liu, G, Rennert, G, Albanes, D, Aldrich, MC, Tardon, A, 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, Bickeboller, H, Ness, AR, Thomas, S, Le, ML, Schabath, MB, Wunsch-Filho, V, Tajara, EH, Andrew, AS, Clifford, GM, Lazarus, P, Grankvist, K, Johansson, M, Arnold, S, Melander, O, Brunnstrom, H, Boccia, S , Cadoni, G, Timens, W, Obeidat, M, 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, no. 3, pp. 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, C.

AU - Ferreiro-Iglesias, A.

AU - McKay, J. D.

AU - Bosse, Y.

AU - Johansson, M.

AU - Gaborieau, V.

AU - Landi, M. T.

AU - Christiani, D. C.

AU - Caporaso, N. C.

AU - Bojesen, S. E.

AU - Amos, C. I.

AU - Shete, S.

AU - Liu, G.

AU - Rennert, G.

AU - Albanes, D.

AU - Aldrich, M. C.

AU - Tardon, A.

AU - Chen, C.

AU - Triantafillos, L.

AU - Field, J. K.

AU - Teare, M. D.

AU - Kiemeney, L. A.

AU - Diergaarde, B.

AU - Ferris, R. L.

AU - Zienolddiny, S.

AU - Lam, S.

AU - Olshan, A. F.

AU - Weissler, M. C.

AU - Lacko, M.

AU - Risch, A.

AU - Bickeboller, H.

AU - Ness, A. R.

AU - Thomas, S.

AU - Le, Marchand L.

AU - Schabath, M. B.

AU - Wunsch-Filho, V.

AU - Tajara, E. H.

AU - Andrew, A. S.

AU - Clifford, G. M.

AU - Lazarus, P.

AU - Grankvist, K.

AU - Johansson, M.

AU - Arnold, S.

AU - Melander, O.

AU - Brunnstrom, H.

AU - Boccia, Stefania

AU - Cadoni, Gabriella

AU - Timens, W.

AU - Obeidat, M.

AU - Xiao, X.

AU - Houlston, R. S.

AU - Hung, R. J.

AU - Brennan, P.

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 - https://publicatt.unicatt.it/handle/10807/175363

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UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85102647478&origin=inward

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

IS - 3

ER -

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

Abstract

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Keywords

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