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 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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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
Article numberdjv037
Number of pages4
JournalJournal of the National Cancer Institute
Issue number5
Early online date2 Apr 2015
Publication statusPublished - 1 May 2015

Bibliographical note

© The Author 2015. Published by Oxford University Press.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

This work was supported the National Institutes of Health (R01CA092039 05/05S1) and the National Institute of Dental and Craniofacial Research (1R03DE020116).

The authors thank all of the participants who took part in this research and the funders and technical staff who made this study possible. We acknowledge and thank Simone Benhamou (INSERM, France) for sample contributions. We also acknowledge and thank The Cancer Genome Atlas initiative, whose data
contributed heavily to this study.


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