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 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 (Lead / Corresponding author)

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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 language	English
Pages (from-to)	1-4
Number of pages	5
Journal	Journal of the National Cancer Institute (JNCI)
Volume	107
Issue number	5
Early online date	2 Apr 2015
DOIs	https://doi.org/10.1093/jnci/djv037
Publication status	Published - 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

UN SDGs

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

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10.1093/jnci/djv037

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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 (JNCI), 107(5), 1-4. https://doi.org/10.1093/jnci/djv037

@article{2259440451cf4f8aa2c84a7ce20bf3f8,

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 = "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",

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}",

note = "This work was supported the National Institutes of Health (R01 CA092039 05/05S1) and the National Institute of Dental and Craniofacial Research (1R03DE020116).",

year = "2015",

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doi = "10.1093/jnci/djv037",

language = "English",

volume = "107",

pages = "1--4",

journal = "Journal of the National Cancer Institute (JNCI)",

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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 (JNCI), vol. 107, no. 5, pp. 1-4. 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

N1 - This work was supported the National Institutes of Health (R01 CA092039 05/05S1) and the National Institute of Dental and Craniofacial Research (1R03DE020116).

PY - 2015/5

Y1 - 2015/5

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 - Adult

KW - Aged

KW - Alcohol Drinking

KW - BRCA2 Protein

KW - Carcinoma, Squamous Cell

KW - Case-Control Studies

KW - Female

KW - Genetic Predisposition to Disease

KW - Head and Neck Neoplasms

KW - Humans

KW - Logistic Models

KW - Male

KW - Middle Aged

KW - Odds Ratio

KW - Polymorphism, Single Nucleotide

KW - Risk Assessment

KW - Risk Factors

KW - Smoking

KW - Journal Article

KW - Research Support, N.I.H., Extramural

U2 - 10.1093/jnci/djv037

DO - 10.1093/jnci/djv037

M3 - Article

C2 - 25838448

SN - 0027-8874

VL - 107

SP - 1

EP - 4

JO - Journal of the National Cancer Institute (JNCI)

JF - Journal of the National Cancer Institute (JNCI)

IS - 5

ER -

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

Abstract

Keywords

UN SDGs

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