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 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; Stefania Boccia; Thangarajan Rajkumar; Tanuja A. Samant; Manoj B. Mahimkar; Keitaro Matsuo; Silvia Franceschi; Graham Byrnes; Paul Brennan; James D. Mckay

doi:10.1093/jnci/djv037

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 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, Stefania Boccia, Thangarajan Rajkumar, Tanuja A. Samant, Manoj B. Mahimkar, Keitaro Matsuo, Silvia Franceschi, Graham Byrnes, Paul Brennan, James D. Mckay

International Agency for Research on Cancer
Genetic Epidemiology Group
University of Edinburgh
National and Kapodistrian University of Athens
Charles University
University of Turin
Cancer Registry of Norway Institute of Population-Based Cancer Research
Centro de Investigación Biomédica en Red
University of Aberdeen
General Hospital of Pordenone
Imperial College London
School of Dentistry
University of Glasgow
Croatian National Institute of Public Health
Trinity College Dublin
University of Bremen
Russian Academy of Medical Sciences - N.N. Blokhin Russian Cancer Research Center
Nofer Institute of Occupational Medicine
Maria Sklodowska-Curie Institute of Oncology
Regional Authority of Public Health
Carol Davila University of Medicine and Pharmacy
Masaryk Memorial Cancer Institute
Palacký University Olomouc
University of Strathclyde
Fundação Oswaldo Cruz
Universidade Federal de Pelotas
Universidade de São Paulo
Icahn School of Medicine at Mount Sinai
National School of Public Health
IRCCS Centro di Riferimento Oncologico - Aviano PN
International Hereditary Cancer Center
Cancer Institute India
Tata Memorial Hospital
Infections and Cancer Epidemiology Group
Biostatistics Group

Research output: Contribution to journal › Article › peer-review

23 Citations (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.

Original language	English
Pages (from-to)	djv037-djv037
Number of pages	4
Journal	Journal of the National Cancer Institute
Volume	107
DOIs	https://doi.org/10.1093/jnci/djv037
Publication status	Published - 2015

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

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

Access to Document

10.1093/jnci/djv037

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, djv037-djv037. https://doi.org/10.1093/jnci/djv037

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title = "A Rare Truncating BRCA2 Variant and Genetic Susceptibility to Upper Aerodigestive Tract Cancer",

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.",

keywords = "GENOME-WIDE ASSOCIATION, HOMOLOGOUS RECOMBINATION, POLYMORPHIC STOP CODON, POPULATION, PREVALENCE, SQUAMOUS-CELL CARCINOMA, GENOME-WIDE ASSOCIATION, HOMOLOGOUS RECOMBINATION, POLYMORPHIC STOP CODON, POPULATION, PREVALENCE, SQUAMOUS-CELL CARCINOMA",

author = "Manon Delahaye-Sourdeix and Devasena Anantharaman and Timofeeva, \{Maria N.\} and Val{\'e}rie Gaborieau and Am{\'e}lie Chabrier and Vall{\'e}e, \{Maxime P.\} and Pagona Lagiou and Ivana Holc{\'a}tov{\'a} and Lorenzo Richiardi and Kristina Kjaerheim and Antonio Agudo and Xavier Castellsagu{\'e} and Macfarlane, \{Tatiana V.\} and Luigi Barzan and Cristina Canova and Thakker, \{Nalin S.\} and Conway, \{David I.\} and Ariana Znaor and Healy, \{Claire M.\} and Wolfgang Ahrens and David Zaridze and Neonilia Szeszenia-Dabrowska and Jolanta Lissowska and Eleonora Fabianova and Mates, \{Ioan Nicolae\} and Vladimir Bencko and Lenka Foretova and Vladimir Janout and Curado, \{Maria Paula\} and Sergio Koifman and Ana Menezes and Victor W{\"u}nsch-Filho and Jos{\'e} Eluf-Neto and Paolo Boffetta and \{Fern{\'a}ndez Garrote\}, Leticia and Jerry Polesel and Marcin Lener and Ewa Jaworowska and Jan Lubi{\'n}ski and Stefania Boccia and Thangarajan Rajkumar and Samant, \{Tanuja A.\} and Mahimkar, \{Manoj B.\} and Keitaro Matsuo and Silvia Franceschi and Graham Byrnes and Paul Brennan and Mckay, \{James D.\}",

year = "2015",

doi = "10.1093/jnci/djv037",

language = "English",

volume = "107",

pages = "djv037--djv037",

journal = "Journal of the National Cancer Institute",

issn = "0027-8874",

publisher = "Oxford University Press",

}

Delahaye-Sourdeix, M, Anantharaman, D, Timofeeva, MN, Gaborieau, V, Chabrier, A, Vallée, MP, Lagiou, P, Holcátová, I, Richiardi, L, Kjaerheim, K, Agudo, A, Castellsagué, X, Macfarlane, TV, Barzan, L, Canova, C, Thakker, NS, Conway, DI, Znaor, A, Healy, CM, Ahrens, W, Zaridze, D, Szeszenia-Dabrowska, N, Lissowska, J, Fabianova, E, Mates, IN, Bencko, V, Foretova, L, Janout, V, Curado, MP, Koifman, S, Menezes, A, Wünsch-Filho, V, Eluf-Neto, J, Boffetta, P, Fernández Garrote, L, Polesel, J, Lener, M, Jaworowska, E, Lubiński, J, Boccia, S, Rajkumar, T, Samant, TA, Mahimkar, MB, Matsuo, K, Franceschi, S, Byrnes, G, Brennan, P & Mckay, JD 2015, 'A Rare Truncating BRCA2 Variant and Genetic Susceptibility to Upper Aerodigestive Tract Cancer', Journal of the National Cancer Institute, vol. 107, pp. djv037-djv037. https://doi.org/10.1093/jnci/djv037

TY - JOUR

T1 - A Rare Truncating BRCA2 Variant and Genetic Susceptibility to Upper Aerodigestive Tract Cancer

AU - Delahaye-Sourdeix, Manon

AU - Anantharaman, Devasena

AU - Timofeeva, Maria N.

AU - Gaborieau, Valérie

AU - Chabrier, Amélie

AU - Vallée, Maxime P.

AU - Lagiou, Pagona

AU - Holcátová, Ivana

AU - Richiardi, Lorenzo

AU - Kjaerheim, Kristina

AU - Agudo, Antonio

AU - Castellsagué, Xavier

AU - Macfarlane, Tatiana V.

AU - Barzan, Luigi

AU - Canova, Cristina

AU - Thakker, Nalin S.

AU - Conway, David I.

AU - Znaor, Ariana

AU - Healy, Claire M.

AU - Ahrens, Wolfgang

AU - Zaridze, David

AU - Szeszenia-Dabrowska, Neonilia

AU - Lissowska, Jolanta

AU - Fabianova, Eleonora

AU - Mates, Ioan Nicolae

AU - Bencko, Vladimir

AU - Foretova, Lenka

AU - Janout, Vladimir

AU - Curado, Maria Paula

AU - Koifman, Sergio

AU - Menezes, Ana

AU - Wünsch-Filho, Victor

AU - Eluf-Neto, José

AU - Boffetta, Paolo

AU - Fernández Garrote, Leticia

AU - Polesel, Jerry

AU - Lener, Marcin

AU - Jaworowska, Ewa

AU - Lubiński, Jan

AU - Boccia, Stefania

AU - Rajkumar, Thangarajan

AU - Samant, Tanuja A.

AU - Mahimkar, Manoj B.

AU - Matsuo, Keitaro

AU - Franceschi, Silvia

AU - Byrnes, Graham

AU - Brennan, Paul

AU - Mckay, James D.

PY - 2015

Y1 - 2015

N2 - 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.

AB - 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.

KW - GENOME-WIDE ASSOCIATION

KW - HOMOLOGOUS RECOMBINATION

KW - POLYMORPHIC STOP CODON

KW - POPULATION

KW - PREVALENCE

KW - SQUAMOUS-CELL CARCINOMA

KW - GENOME-WIDE ASSOCIATION

KW - HOMOLOGOUS RECOMBINATION

KW - POLYMORPHIC STOP CODON

KW - POPULATION

KW - PREVALENCE

KW - SQUAMOUS-CELL CARCINOMA

UR - http://hdl.handle.net/10807/70352

U2 - 10.1093/jnci/djv037

DO - 10.1093/jnci/djv037

M3 - Article

SN - 0027-8874

VL - 107

SP - djv037-djv037

JO - Journal of the National Cancer Institute

JF - Journal of the National Cancer Institute

ER -

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

Abstract

UN SDGs

Keywords

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