The 12p13.33/RAD52 Locus and Genetic Susceptibility to Squamous Cell Cancers of Upper Aerodigestive Tract

M Delahaye Sourdeix; J Oliver; Mn Timofeeva; V Gaborieau; M Johansson; A Chabrier; Mb Wozniak; Brenner; Mp Vallée; D Anantharaman; P Lagiou; I Holcátová; L Richiardi; K Kjaerheim; A Agudo; X Castellsagué; Tv Macfarlane; L Barzan; C Canova; Ns Thakker; Di Conway; A Znaor; Cm Healy; W Ahrens; D Zaridze; N Szeszenia Dabrowska; J Lissowska; E Fabianova; In Mates; V Bencko; L Foretova; V Janout; Mp Curado; S Koifman; A Menezes; V Wünsch Filho; J Eluf Neto; P Boffetta; Lf Garrote; D Serraino; M Lener; E Jaworowska; J Lubiński; Stefania Boccia; T Rajkumar; Ta Samant; Mb Mahimkar; K Matsuo; S Franceschi; G Byrnes; P Brennan; Jd Mckay

doi:10.1371/journal.pone.0117639

The 12p13.33/RAD52 Locus and Genetic Susceptibility to Squamous Cell Cancers of Upper Aerodigestive Tract

M Delahaye Sourdeix
, J Oliver
, Mn Timofeeva
, V Gaborieau
, M Johansson
, A Chabrier
, Mb Wozniak
, Brenner
, Mp Vallée
, D Anantharaman
, P Lagiou
, I Holcátová
, L Richiardi
, K Kjaerheim
, A Agudo
, X Castellsagué
, Tv Macfarlane
, L Barzan
, C Canova
, Ns Thakker

Di Conway, A Znaor, Cm Healy, W Ahrens, D Zaridze, N Szeszenia Dabrowska, J Lissowska, E Fabianova, In Mates, V Bencko, L Foretova, V Janout, Mp Curado, S Koifman, A Menezes, V Wünsch Filho, J Eluf Neto, P Boffetta, Lf Garrote, D Serraino, M Lener, E Jaworowska, J Lubiński, Stefania Boccia, T Rajkumar, Ta Samant, Mb Mahimkar, K Matsuo, S Franceschi, G Byrnes, P Brennan, Jd Mckay

Research output: Contribution to journal › Article

9 Citations (Scopus)

Abstract

Genetic variants located within the 12p13.33/RAD52 locus have been associated with lung squamous cell carcinoma (LUSC). Here, within 5,947 UADT cancers and 7,789 controls from 9 different studies, we found rs10849605, a common intronic variant in RAD52, to be also associated with upper aerodigestive tract (UADT) squamous cell carcinoma cases (OR = 1.09, 95% CI: 1.04-1.15, p = 6x10(-4)). We additionally identified rs10849605 as a RAD52 cis-eQTL inUADT(p = 1x10(-3)) and LUSC (p = 9x10(-4)) tumours, with the UADT/LUSC risk allele correlated with increased RAD52 expression levels. The 12p13.33 locus, encompassing rs10849605/RAD52, was identified as a significant somatic focal copy number amplification in UADT(n = 374, q-value = 0.075) and LUSC (n = 464, q-value = 0.007) tumors and correlated with higher RAD52 tumor expression levels (p = 6x10(-48) and p = 3x10(-29) in UADT and LUSC, respectively). In combination, these results implicate increased RAD52 expression in both genetic susceptibility and tumorigenesis of UADT and LUSC tumors.

Original language	English
Pages (from-to)	e0117639-e0117639
Number of pages	12
Journal	PLoS One
Volume	10
Issue number	3
DOIs	https://doi.org/10.1371/journal.pone.0117639
Publication status	Published - 2015

UN SDGs

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

SDG 3 Good Health and Well-being

All Science Journal Classification (ASJC) codes

General

Keywords

BRCA2
BREAK REPAIR
DIFFERENTIAL EXPRESSION ANALYSIS
GENOME-WIDE ASSOCIATION
HOMOLOGOUS RECOMBINATION
LUNG-Cancer
RAD52 INACTIVATION
RNA-SEQ

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10.1371/journal.pone.0117639

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Delahaye Sourdeix, M., Oliver, J., Timofeeva, M., Gaborieau, V., Johansson, M., Chabrier, A., Wozniak, M., Brenner, Vallée, M., Anantharaman, D., Lagiou, P., Holcátová, I., Richiardi, L., Kjaerheim, K., Agudo, A., Castellsagué, X., Macfarlane, T., Barzan, L., Canova, C., ... Mckay, J. (2015). The 12p13.33/RAD52 Locus and Genetic Susceptibility to Squamous Cell Cancers of Upper Aerodigestive Tract. PLoS One, 10(3), e0117639-e0117639. https://doi.org/10.1371/journal.pone.0117639

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title = "The 12p13.33/RAD52 Locus and Genetic Susceptibility to Squamous Cell Cancers of Upper Aerodigestive Tract",

abstract = "Genetic variants located within the 12p13.33/RAD52 locus have been associated with lung squamous cell carcinoma (LUSC). Here, within 5,947 UADT cancers and 7,789 controls from 9 different studies, we found rs10849605, a common intronic variant in RAD52, to be also associated with upper aerodigestive tract (UADT) squamous cell carcinoma cases (OR = 1.09, 95\% CI: 1.04-1.15, p = 6x10(-4)). We additionally identified rs10849605 as a RAD52 cis-eQTL inUADT(p = 1x10(-3)) and LUSC (p = 9x10(-4)) tumours, with the UADT/LUSC risk allele correlated with increased RAD52 expression levels. The 12p13.33 locus, encompassing rs10849605/RAD52, was identified as a significant somatic focal copy number amplification in UADT(n = 374, q-value = 0.075) and LUSC (n = 464, q-value = 0.007) tumors and correlated with higher RAD52 tumor expression levels (p = 6x10(-48) and p = 3x10(-29) in UADT and LUSC, respectively). In combination, these results implicate increased RAD52 expression in both genetic susceptibility and tumorigenesis of UADT and LUSC tumors.",

keywords = "BRCA2, BREAK REPAIR, DIFFERENTIAL EXPRESSION ANALYSIS, GENOME-WIDE ASSOCIATION, HOMOLOGOUS RECOMBINATION, LUNG-Cancer, RAD52 INACTIVATION, RNA-SEQ, BRCA2, BREAK REPAIR, DIFFERENTIAL EXPRESSION ANALYSIS, GENOME-WIDE ASSOCIATION, HOMOLOGOUS RECOMBINATION, LUNG-Cancer, RAD52 INACTIVATION, RNA-SEQ",

author = "\{Delahaye Sourdeix\}, M and J Oliver and Mn Timofeeva and V Gaborieau and M Johansson and A Chabrier and Mb Wozniak and Brenner and Mp Vall{\'e}e and D Anantharaman and P Lagiou and I Holc{\'a}tov{\'a} and L Richiardi and K Kjaerheim and A Agudo and X Castellsagu{\'e} and Tv Macfarlane and L Barzan and C Canova and Ns Thakker and Di Conway and A Znaor and Cm Healy and W Ahrens and D Zaridze and \{Szeszenia Dabrowska\}, N and J Lissowska and E Fabianova and In Mates and V Bencko and L Foretova and V Janout and Mp Curado and S Koifman and A Menezes and \{W{\"u}nsch Filho\}, V and \{Eluf Neto\}, J and P Boffetta and Lf Garrote and D Serraino and M Lener and E Jaworowska and J Lubi{\'n}ski and Stefania Boccia and T Rajkumar and Ta Samant and Mb Mahimkar and K Matsuo and S Franceschi and G Byrnes and P Brennan and Jd Mckay",

year = "2015",

doi = "10.1371/journal.pone.0117639",

language = "English",

volume = "10",

pages = "e0117639--e0117639",

journal = "PLoS One",

issn = "1932-6203",

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number = "3",

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Delahaye Sourdeix, M, Oliver, J, Timofeeva, M, Gaborieau, V, Johansson, M, Chabrier, A, Wozniak, M, Brenner, Vallée, M, Anantharaman, D, Lagiou, P, Holcátová, I, Richiardi, L, Kjaerheim, K, Agudo, A, Castellsagué, X, Macfarlane, T, Barzan, L, Canova, C, Thakker, N, Conway, D, Znaor, A, Healy, C, Ahrens, W, Zaridze, D, Szeszenia Dabrowska, N, Lissowska, J, Fabianova, E, Mates, I, Bencko, V, Foretova, L, Janout, V, Curado, M, Koifman, S, Menezes, A, Wünsch Filho, V, Eluf Neto, J, Boffetta, P, Garrote, L, Serraino, D, Lener, M, Jaworowska, E, Lubiński, J, Boccia, S, Rajkumar, T, Samant, T, Mahimkar, M, Matsuo, K, Franceschi, S, Byrnes, G, Brennan, P & Mckay, J 2015, 'The 12p13.33/RAD52 Locus and Genetic Susceptibility to Squamous Cell Cancers of Upper Aerodigestive Tract', PLoS One, vol. 10, no. 3, pp. e0117639-e0117639. https://doi.org/10.1371/journal.pone.0117639

TY - JOUR

T1 - The 12p13.33/RAD52 Locus and Genetic Susceptibility to Squamous Cell Cancers of Upper Aerodigestive Tract

AU - Delahaye Sourdeix, M

AU - Oliver, J

AU - Timofeeva, Mn

AU - Gaborieau, V

AU - Johansson, M

AU - Chabrier, A

AU - Wozniak, Mb

AU - Brenner,

AU - Vallée, Mp

AU - Anantharaman, D

AU - Lagiou, P

AU - Holcátová, I

AU - Richiardi, L

AU - Kjaerheim, K

AU - Agudo, A

AU - Castellsagué, X

AU - Macfarlane, Tv

AU - Barzan, L

AU - Canova, C

AU - Thakker, Ns

AU - Conway, Di

AU - Znaor, A

AU - Healy, Cm

AU - Ahrens, W

AU - Zaridze, D

AU - Szeszenia Dabrowska, N

AU - Lissowska, J

AU - Fabianova, E

AU - Mates, In

AU - Bencko, V

AU - Foretova, L

AU - Janout, V

AU - Curado, Mp

AU - Koifman, S

AU - Menezes, A

AU - Wünsch Filho, V

AU - Eluf Neto, J

AU - Boffetta, P

AU - Garrote, Lf

AU - Serraino, D

AU - Lener, M

AU - Jaworowska, E

AU - Lubiński, J

AU - Boccia, Stefania

AU - Rajkumar, T

AU - Samant, Ta

AU - Mahimkar, Mb

AU - Matsuo, K

AU - Franceschi, S

AU - Byrnes, G

AU - Brennan, P

AU - Mckay, Jd

PY - 2015

Y1 - 2015

N2 - Genetic variants located within the 12p13.33/RAD52 locus have been associated with lung squamous cell carcinoma (LUSC). Here, within 5,947 UADT cancers and 7,789 controls from 9 different studies, we found rs10849605, a common intronic variant in RAD52, to be also associated with upper aerodigestive tract (UADT) squamous cell carcinoma cases (OR = 1.09, 95% CI: 1.04-1.15, p = 6x10(-4)). We additionally identified rs10849605 as a RAD52 cis-eQTL inUADT(p = 1x10(-3)) and LUSC (p = 9x10(-4)) tumours, with the UADT/LUSC risk allele correlated with increased RAD52 expression levels. The 12p13.33 locus, encompassing rs10849605/RAD52, was identified as a significant somatic focal copy number amplification in UADT(n = 374, q-value = 0.075) and LUSC (n = 464, q-value = 0.007) tumors and correlated with higher RAD52 tumor expression levels (p = 6x10(-48) and p = 3x10(-29) in UADT and LUSC, respectively). In combination, these results implicate increased RAD52 expression in both genetic susceptibility and tumorigenesis of UADT and LUSC tumors.

AB - Genetic variants located within the 12p13.33/RAD52 locus have been associated with lung squamous cell carcinoma (LUSC). Here, within 5,947 UADT cancers and 7,789 controls from 9 different studies, we found rs10849605, a common intronic variant in RAD52, to be also associated with upper aerodigestive tract (UADT) squamous cell carcinoma cases (OR = 1.09, 95% CI: 1.04-1.15, p = 6x10(-4)). We additionally identified rs10849605 as a RAD52 cis-eQTL inUADT(p = 1x10(-3)) and LUSC (p = 9x10(-4)) tumours, with the UADT/LUSC risk allele correlated with increased RAD52 expression levels. The 12p13.33 locus, encompassing rs10849605/RAD52, was identified as a significant somatic focal copy number amplification in UADT(n = 374, q-value = 0.075) and LUSC (n = 464, q-value = 0.007) tumors and correlated with higher RAD52 tumor expression levels (p = 6x10(-48) and p = 3x10(-29) in UADT and LUSC, respectively). In combination, these results implicate increased RAD52 expression in both genetic susceptibility and tumorigenesis of UADT and LUSC tumors.

KW - BRCA2

KW - BREAK REPAIR

KW - DIFFERENTIAL EXPRESSION ANALYSIS

KW - GENOME-WIDE ASSOCIATION

KW - HOMOLOGOUS RECOMBINATION

KW - LUNG-Cancer

KW - RAD52 INACTIVATION

KW - RNA-SEQ

KW - BRCA2

KW - BREAK REPAIR

KW - DIFFERENTIAL EXPRESSION ANALYSIS

KW - GENOME-WIDE ASSOCIATION

KW - HOMOLOGOUS RECOMBINATION

KW - LUNG-Cancer

KW - RAD52 INACTIVATION

KW - RNA-SEQ

UR - https://publicatt.unicatt.it/handle/10807/70404

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U2 - 10.1371/journal.pone.0117639

DO - 10.1371/journal.pone.0117639

M3 - Article

SN - 1932-6203

VL - 10

SP - e0117639-e0117639

JO - PLoS One

JF - PLoS One

IS - 3

ER -

The 12p13.33/RAD52 Locus and Genetic Susceptibility to Squamous Cell Cancers of Upper Aerodigestive Tract

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