PLoS ONE (Jan 2015)

The 12p13.33/RAD52 locus and genetic susceptibility to squamous cell cancers of upper aerodigestive tract.

  • Manon Delahaye-Sourdeix,
  • Javier Oliver,
  • Maria N Timofeeva,
  • Valérie Gaborieau,
  • Mattias Johansson,
  • Amélie Chabrier,
  • Magdalena B Wozniak,
  • Darren R Brenner,
  • Maxime P Vallée,
  • Devasena Anantharaman,
  • Pagona Lagiou,
  • Ivana Holcátová,
  • Lorenzo Richiardi,
  • Kristina Kjaerheim,
  • Antonio Agudo,
  • Xavier Castellsagué,
  • Tatiana V Macfarlane,
  • Luigi Barzan,
  • Cristina Canova,
  • Nalin S Thakker,
  • David I Conway,
  • Ariana Znaor,
  • Claire M Healy,
  • Wolfgang Ahrens,
  • David Zaridze,
  • Neonilia Szeszenia-Dabrowska,
  • Jolanta Lissowska,
  • Eleonora Fabianova,
  • Ioan Nicolae Mates,
  • Vladimir Bencko,
  • Lenka Foretova,
  • Vladimir Janout,
  • Maria Paula Curado,
  • Sergio Koifman,
  • Ana Menezes,
  • Victor Wünsch-Filho,
  • José Eluf-Neto,
  • Paolo Boffetta,
  • Leticia Fernández Garrote,
  • Diego Serraino,
  • Marcin Lener,
  • Ewa Jaworowska,
  • Jan Lubiński,
  • Stefania Boccia,
  • Thangarajan Rajkumar,
  • Tanuja A Samant,
  • Manoj B Mahimkar,
  • Keitaro Matsuo,
  • Silvia Franceschi,
  • Graham Byrnes,
  • Paul Brennan,
  • James D McKay

DOI
https://doi.org/10.1371/journal.pone.0117639
Journal volume & issue
Vol. 10, no. 3
p. e0117639

Abstract

Read online

Genetic variants located within the 12p13.33/RAD52 locus have been associated with lung squamous cell carcinoma (LUSC). Here, within 5,947 UADT cancers and 7,789 controls from 9 different studies, we found rs10849605, a common intronic variant in RAD52, to be also associated with upper aerodigestive tract (UADT) squamous cell carcinoma cases (OR = 1.09, 95% CI: 1.04-1.15, p = 6x10(-4)). We additionally identified rs10849605 as a RAD52 cis-eQTL inUADT(p = 1x10(-3)) and LUSC (p = 9x10(-4)) tumours, with the UADT/LUSC risk allele correlated with increased RAD52 expression levels. The 12p13.33 locus, encompassing rs10849605/RAD52, was identified as a significant somatic focal copy number amplification in UADT(n = 374, q-value = 0.075) and LUSC (n = 464, q-value = 0.007) tumors and correlated with higher RAD52 tumor expression levels (p = 6x10(-48) and p = 3x10(-29) in UADT and LUSC, respectively). In combination, these results implicate increased RAD52 expression in both genetic susceptibility and tumorigenesis of UADT and LUSC tumors.