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. FieldM. 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^*

^*Autore corrispondente per questo lavoro

Risultato della ricerca: Contributo in rivista › Articolo

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	Inglese
pagine (da-a)	e1009254-e1009254
Rivista	PLoS Genetics
Volume	17
Numero di pubblicazione	3
DOI	https://doi.org/10.1371/journal.pgen.1009254
Stato di pubblicazione	Pubblicato - 2021

All Science Journal Classification (ASJC) codes

Ecologia, Evoluzione, Comportamento e Sistematica
Biologia Molecolare
Genetica
Genetica (clinica)
Ricerca sul Cancro

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., 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, n. 3, 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, 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

All Science Journal Classification (ASJC) codes

Keywords

OSS delle Nazioni Unite

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