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Olle Melander

Principal investigator

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

Author

  • 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
  • Gadi Rennert
  • Demetrios Albanes
  • Melinda C Aldrich
  • Adonina Tardon
  • Chu 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

Summary, in English

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.

Department/s

  • EXODIAB: Excellence in Diabetes Research in Sweden
  • EpiHealth: Epidemiology for Health
  • Cardiovascular Research - Hypertension
  • Pathology, Lund
  • LUCC - Lund University Cancer Centre
  • Improved diagnostics and prognostics of lung cancer and metastases to the lungs

Publishing year

2021-03-05

Language

English

Pages

1009254-1009254

Publication/Series

PLoS Genetics

Volume

17

Issue

3

Document type

Journal article

Publisher

Public Library of Science

Topic

  • Cancer and Oncology

Status

Epub

Research group

  • Cardiovascular Research - Hypertension
  • Improved diagnostics and prognostics of lung cancer and metastases to the lungs

ISBN/ISSN/Other

  • ISSN: 1553-7404