A Rare Truncating BRCA2 Variant and Genetic Susceptibility to Upper Aerodigestive Tract Cancer

Stefania Boccia, 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. HealyWolfgang 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, Jerry Polesel, Marcin Lener, Ewa Jaworowska, Jan Lubiński, Tanuja A. Samant, Manoj B. Mahimkar, Keitaro Matsuo, Silvia Franceschi, Graham Byrnes, Paul Brennan, James D. Mckay

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23 Citazioni (Scopus)

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.
Lingua originaleEnglish
pagine (da-a)djv037-djv037
Numero di pagine4
RivistaJournal of the National Cancer Institute
Volume107
DOI
Stato di pubblicazionePubblicato - 2015

Keywords

  • GENOME-WIDE ASSOCIATION
  • HOMOLOGOUS RECOMBINATION
  • POLYMORPHIC STOP CODON
  • POPULATION
  • PREVALENCE
  • SQUAMOUS-CELL CARCINOMA

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