A rare truncating BRCA2 variant and genetic susceptibility to upper aerodigestive tract cancer

Manon Delahaye-Sourdeix, Devasena Anantharaman, Maria N Timofeeva, Valérie Gaborieau, Amélie Chabrier, Maxime P Vallée, 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 AhrensDavid 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, Jerry Polesel, 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

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Abstract

Deleterious BRCA2 genetic variants markedly increase risk of developing breast cancer. A rare truncating BRCA2 genetic variant, rs11571833 (K3326X), has been associated with a 2.5-fold risk of lung squamous cell carcinoma but only a modest 26% increase in breast cancer risk. We analyzed the association between BRCA2 SNP rs11571833 and upper aerodigestive tract (UADT) cancer risk with multivariable unconditional logistic regression adjusted by sex and combinations of study and country for 5942 UADT squamous cell carcinoma case patients and 8086 control patients from nine different studies. All statistical tests were two-sided. rs11571833 was associated with UADT cancers (odds ratio = 2.53, 95% confidence interval = 1.89 to 3.38, P = 3x10(-10)) and was present in European, Latin American, and Indian populations but extremely rare in Japanese populations. The association appeared more apparent in smokers (current or former) compared with never smokers (P het = .026). A robust association between a truncating BRCA2 variant and UADT cancer risk suggests that treatment strategies orientated towards BRCA2 mutations may warrant further investigation in UADT tumors.

Original languageEnglish
Pages (from-to)1-4
Number of pages5
JournalJournal of the National Cancer Institute
Volume107
Issue number5
Early online date2 Apr 2015
DOIs
Publication statusPublished - May 2015

Keywords

  • Adult
  • Aged
  • Alcohol Drinking
  • BRCA2 Protein
  • Carcinoma, Squamous Cell
  • Case-Control Studies
  • Female
  • Genetic Predisposition to Disease
  • Head and Neck Neoplasms
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • Odds Ratio
  • Polymorphism, Single Nucleotide
  • Risk Assessment
  • Risk Factors
  • Smoking
  • Journal Article
  • Research Support, N.I.H., Extramural

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  • Cite this

    Delahaye-Sourdeix, M., Anantharaman, D., Timofeeva, M. N., Gaborieau, V., Chabrier, A., Vallée, M. P., Lagiou, P., Holcátová, I., Richiardi, L., Kjaerheim, K., Agudo, A., Castellsagué, X., Macfarlane, T. V., Barzan, L., Canova, C., Thakker, N. S., Conway, D. I., Znaor, A., Healy, C. M., ... McKay, J. D. (2015). A rare truncating BRCA2 variant and genetic susceptibility to upper aerodigestive tract cancer. Journal of the National Cancer Institute, 107(5), 1-4. https://doi.org/10.1093/jnci/djv037