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

Lesseur, Corina ; Ferreiro-Iglesias, Aida ; McKay, James D ; Bossé, Yohan ; Johansson, Mattias ; Gaborieau, Valerie ; Landi, Maria Teresa ; Christiani, David C ; Caporaso, Neil C and Bojesen, Stig E , et al. (2021) In PLoS Genetics 17(3).
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... (More)

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.

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Contribution to journal
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published
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PLoS Genetics
volume
17
issue
3
article number
e1009254
publisher
Public Library of Science (PLoS)
external identifiers
  • pmid:33667223
  • scopus:85102647478
ISSN
1553-7404
DOI
10.1371/journal.pgen.1009254
language
English
LU publication?
yes
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f1281cc1-b007-45f2-87f6-45aaffe1c8be
date added to LUP
2021-03-11 14:56:34
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2023-04-11 07:38:42
@article{f1281cc1-b007-45f2-87f6-45aaffe1c8be,
  abstract     = {{<p>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&lt;5x10-8) aerodigestive SqCC susceptibility loci in the 2q33.1 region (rs56321285, TMEM273). Additionally, three previously unknown loci reached suggestive significance (Pmeta&lt;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.</p>}},
  author       = {{Lesseur, Corina and Ferreiro-Iglesias, Aida and McKay, James D and Bossé, Yohan and Johansson, Mattias and Gaborieau, Valerie and Landi, Maria Teresa and Christiani, David C and Caporaso, Neil C and Bojesen, Stig E and Amos, Christopher I and Shete, Sanjay and Liu, Geoffrey and Rennert, Gadi and Albanes, Demetrios and Aldrich, Melinda C and Tardon, Adonina and Chen, Chu and Triantafillos, Liloglou and Field, John K and Teare, Marion Dawn and Kiemeney, Lambertus A and Diergaarde, Brenda and Ferris, Robert L and Zienolddiny, Shanbeh and Lam, Stephen and Olshan, Andrew F and Weissler, Mark C and Lacko, Martin and Risch, Angela and Bickeböller, Heike and Ness, Andy R and Thomas, Steve and Le Marchand, Loic and Schabath, Matthew B and Wünsch-Filho, Victor and Tajara, Eloiza H and Andrew, Angeline S and Clifford, Gary M and Lazarus, Philip and Grankvist, Kjell and Johansson, Mikael and Arnold, Susanne and Melander, Olle and Brunnström, Hans and Boccia, Stefania and Cadoni, Gabriella and Timens, Wim and Obeidat, Ma'en and Xiao, Xiangjun}},
  issn         = {{1553-7404}},
  language     = {{eng}},
  month        = {{03}},
  number       = {{3}},
  publisher    = {{Public Library of Science (PLoS)}},
  series       = {{PLoS Genetics}},
  title        = {{Genome-wide association meta-analysis identifies pleiotropic risk loci for aerodigestive squamous cell cancers}},
  url          = {{http://dx.doi.org/10.1371/journal.pgen.1009254}},
  doi          = {{10.1371/journal.pgen.1009254}},
  volume       = {{17}},
  year         = {{2021}},
}