A sequence variant at 4p16.3 confers susceptibility to urinary bladder cancer

Kiemeney LA; P Sulem; S Besenbacher; Vermeulen SH; A Sigurdsson; G Thorleifsson; Gudbjartsson DF; Stacey SN; J Gudmundsson; C Zanon; J Kostic; G Masson; H Bjarnason; Palsson ST; Skarphedinsson OB; Gudjonsson SA; Witjes JA; Grotenhuis AJ; Verhaegh GW; Bishop DT; Sak SC; A Choudhury; F Elliott; Barrett JH; Hurst CD; de Verdier PJ; C Ryk; P Rudnai; E Gurzau; K Koppova; Paolo VINEIS; Silvia POLIDORO; Simonetta GUARRERA; Carlotta SACERDOTE; M Campagna; D Placidi; C Arici; Zeegers MP; E Kellen; Gutierrez BS; Sanz Velez JI; Zalabardo M Sanchez; G Valdivia; Garcia Prats MD; Hengstler JG; M Blaszkewicz; H Dietrich; Ophoff RA; van den Berg LH; K Alexiusdottir; K Kristjansson; G Geirsson; S Nikulasson; V Petursdottir; A Kong; T Thorgeirsson; Mungan NA; A Lindblom; van Es MA; S Porru; F Buntinx; K Golka; Mayordomo JI; R Kumar; Giuseppe MATULLO; G Steineck; Kiltie AE; Aben KK; E Jonsson; U Thorsteinsdottir; Knowles MA; T Rafnar; K. Stefansson

doi:10.1038/ng.558

A sequence variant at 4p16.3 confers susceptibility to urinary bladder cancer

Kiemeney LA
, P Sulem
, S Besenbacher
, Vermeulen SH
, A Sigurdsson
, G Thorleifsson
, Gudbjartsson DF
, Stacey SN
, J Gudmundsson
, C Zanon
, J Kostic
, G Masson
, H Bjarnason
, Palsson ST
, Skarphedinsson OB
, Gudjonsson SA
, Witjes JA
, Grotenhuis AJ
, Verhaegh GW
, Bishop DT

Sak SC, A Choudhury, F Elliott, Barrett JH, Hurst CD, de Verdier PJ, C Ryk, P Rudnai, E Gurzau, K Koppova, Paolo VINEIS, Silvia POLIDORO, Simonetta GUARRERA, Carlotta SACERDOTE, M Campagna, D Placidi, C Arici, Zeegers MP, E Kellen, Gutierrez BS, Sanz Velez JI, Zalabardo M Sanchez, G Valdivia, Garcia Prats MD, Hengstler JG, M Blaszkewicz, H Dietrich, Ophoff RA, van den Berg LH, K Alexiusdottir, K Kristjansson, G Geirsson, S Nikulasson, V Petursdottir, A Kong, T Thorgeirsson, Mungan NA, A Lindblom, van Es MA, S Porru, F Buntinx, K Golka, Mayordomo JI, R Kumar, Giuseppe MATULLO, G Steineck, Kiltie AE, Aben KK, E Jonsson, U Thorsteinsdottir, Knowles MA, T Rafnar, K. Stefansson

Risultato della ricerca: Contributo su rivista › Articolo in rivista › peer review

Abstract

Previously, we reported germline DNA variants associated with risk of urinary bladder cancer (UBC) in Dutch and Icelandic subjects. Here we expanded the Icelandic sample set and tested the top 20 markers from the combined analysis in several European case-control sample sets, with a total of 4,739 cases and 45,549 controls. The T allele of rs798766 on 4p16.3 was found to associate with UBC (odds ratio = 1.24, P = 9.9 x 10(-12)). rs798766 is located in an intron of TACC3, 70 kb from FGFR3, which often harbors activating somatic mutations in low-grade, noninvasive UBC. Notably, rs798766[T] shows stronger association with low-grade and low-stage UBC than with more aggressive forms of the disease and is associated with higher risk of recurrence in low-grade stage Ta tumors. The frequency of rs798766[T] is higher in Ta tumors that carry an activating mutation in FGFR3 than in Ta tumors with wild-type FGFR3. Our results show a link between germline variants, somatic mutations of FGFR3 and risk of UBC

Lingua originale	Inglese
pagine (da-a)	415-419
Numero di pagine	5
Rivista	Nature Genetics
Volume	42
Numero di pubblicazione	5
DOI	https://doi.org/10.1038/ng.558
Stato di pubblicazione	Pubblicato - 2010

Keywords

FGFR3
bladder cancer
genome-wide association study

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10.1038/ng.558

https://hdl.handle.net/11579/223148

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LA, K., Sulem, P., Besenbacher, S., SH, V., Sigurdsson, A., Thorleifsson, G., DF, G., SN, S., Gudmundsson, J., Zanon, C., Kostic, J., Masson, G., Bjarnason, H., ST, P., OB, S., SA, G., JA, W., AJ, G., GW, V., ... Stefansson, K. (2010). A sequence variant at 4p16.3 confers susceptibility to urinary bladder cancer. Nature Genetics, 42(5), 415-419. https://doi.org/10.1038/ng.558

@article{a077e28f313743ea9bbff38c4dee48f9,

title = "A sequence variant at 4p16.3 confers susceptibility to urinary bladder cancer",

abstract = "Previously, we reported germline DNA variants associated with risk of urinary bladder cancer (UBC) in Dutch and Icelandic subjects. Here we expanded the Icelandic sample set and tested the top 20 markers from the combined analysis in several European case-control sample sets, with a total of 4,739 cases and 45,549 controls. The T allele of rs798766 on 4p16.3 was found to associate with UBC (odds ratio = 1.24, P = 9.9 x 10(-12)). rs798766 is located in an intron of TACC3, 70 kb from FGFR3, which often harbors activating somatic mutations in low-grade, noninvasive UBC. Notably, rs798766[T] shows stronger association with low-grade and low-stage UBC than with more aggressive forms of the disease and is associated with higher risk of recurrence in low-grade stage Ta tumors. The frequency of rs798766[T] is higher in Ta tumors that carry an activating mutation in FGFR3 than in Ta tumors with wild-type FGFR3. Our results show a link between germline variants, somatic mutations of FGFR3 and risk of UBC",

keywords = "FGFR3, bladder cancer, genome-wide association study, FGFR3, bladder cancer, genome-wide association study",

author = "Kiemeney LA and P Sulem and S Besenbacher and Vermeulen SH and A Sigurdsson and G Thorleifsson and Gudbjartsson DF and Stacey SN and J Gudmundsson and C Zanon and J Kostic and G Masson and H Bjarnason and Palsson ST and Skarphedinsson OB and Gudjonsson SA and Witjes JA and Grotenhuis AJ and Verhaegh GW and Bishop DT and Sak SC and A Choudhury and F Elliott and Barrett JH and Hurst CD and PJ, \{de Verdier\} and C Ryk and P Rudnai and E Gurzau and K Koppova and Paolo VINEIS and Silvia POLIDORO and Simonetta GUARRERA and Carlotta SACERDOTE and M Campagna and D Placidi and C Arici and Zeegers MP and E Kellen and Gutierrez BS and JI, \{Sanz Velez\} and Sanchez, \{Zalabardo M\} and G Valdivia and MD, \{Garcia Prats\} and Hengstler JG and M Blaszkewicz and H Dietrich and Ophoff RA and LH, \{van den Berg\} and K Alexiusdottir and K Kristjansson and G Geirsson and S Nikulasson and V Petursdottir and A Kong and T Thorgeirsson and Mungan NA and A Lindblom and MA, \{van Es\} and S Porru and F Buntinx and K Golka and Mayordomo JI and R Kumar and Giuseppe MATULLO and G Steineck and Kiltie AE and Aben KK and E Jonsson and U Thorsteinsdottir and Knowles MA and T Rafnar and K. Stefansson",

year = "2010",

doi = "10.1038/ng.558",

language = "English",

volume = "42",

pages = "415--419",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "5",

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LA, K, Sulem, P, Besenbacher, S, SH, V, Sigurdsson, A, Thorleifsson, G, DF, G, SN, S, Gudmundsson, J, Zanon, C, Kostic, J, Masson, G, Bjarnason, H, ST, P, OB, S, SA, G, JA, W, AJ, G, GW, V, DT, B, SC, S, Choudhury, A, Elliott, F, JH, B, CD, H, PJ, DV, Ryk, C, Rudnai, P, Gurzau, E, Koppova, K, VINEIS, P, POLIDORO, S, GUARRERA, S, SACERDOTE, C, Campagna, M, Placidi, D, Arici, C, MP, Z, Kellen, E, BS, G, JI, SV, Sanchez, ZM, Valdivia, G, MD, GP, JG, H, Blaszkewicz, M, Dietrich, H, RA, O, LH, VDB, Alexiusdottir, K, Kristjansson, K, Geirsson, G, Nikulasson, S, Petursdottir, V, Kong, A, Thorgeirsson, T, NA, M, Lindblom, A, MA, VE, Porru, S, Buntinx, F, Golka, K, JI, M, Kumar, R, MATULLO, G, Steineck, G, AE, K, KK, A, Jonsson, E, Thorsteinsdottir, U, MA, K, Rafnar, T & Stefansson, K 2010, 'A sequence variant at 4p16.3 confers susceptibility to urinary bladder cancer', Nature Genetics, vol. 42, n. 5, pagg. 415-419. https://doi.org/10.1038/ng.558

TY - JOUR

T1 - A sequence variant at 4p16.3 confers susceptibility to urinary bladder cancer

AU - LA, Kiemeney

AU - Sulem, P

AU - Besenbacher, S

AU - SH, Vermeulen

AU - Sigurdsson, A

AU - Thorleifsson, G

AU - DF, Gudbjartsson

AU - SN, Stacey

AU - Gudmundsson, J

AU - Zanon, C

AU - Kostic, J

AU - Masson, G

AU - Bjarnason, H

AU - ST, Palsson

AU - OB, Skarphedinsson

AU - SA, Gudjonsson

AU - JA, Witjes

AU - AJ, Grotenhuis

AU - GW, Verhaegh

AU - DT, Bishop

AU - SC, Sak

AU - Choudhury, A

AU - Elliott, F

AU - JH, Barrett

AU - CD, Hurst

AU - PJ, de Verdier

AU - Ryk, C

AU - Rudnai, P

AU - Gurzau, E

AU - Koppova, K

AU - VINEIS, Paolo

AU - POLIDORO, Silvia

AU - GUARRERA, Simonetta

AU - SACERDOTE, Carlotta

AU - Campagna, M

AU - Placidi, D

AU - Arici, C

AU - MP, Zeegers

AU - Kellen, E

AU - BS, Gutierrez

AU - JI, Sanz Velez

AU - Sanchez, Zalabardo M

AU - Valdivia, G

AU - MD, Garcia Prats

AU - JG, Hengstler

AU - Blaszkewicz, M

AU - Dietrich, H

AU - RA, Ophoff

AU - LH, van den Berg

AU - Alexiusdottir, K

AU - Kristjansson, K

AU - Geirsson, G

AU - Nikulasson, S

AU - Petursdottir, V

AU - Kong, A

AU - Thorgeirsson, T

AU - NA, Mungan

AU - Lindblom, A

AU - MA, van Es

AU - Porru, S

AU - Buntinx, F

AU - Golka, K

AU - JI, Mayordomo

AU - Kumar, R

AU - MATULLO, Giuseppe

AU - Steineck, G

AU - AE, Kiltie

AU - KK, Aben

AU - Jonsson, E

AU - Thorsteinsdottir, U

AU - MA, Knowles

AU - Rafnar, T

AU - Stefansson, K.

PY - 2010

Y1 - 2010

N2 - Previously, we reported germline DNA variants associated with risk of urinary bladder cancer (UBC) in Dutch and Icelandic subjects. Here we expanded the Icelandic sample set and tested the top 20 markers from the combined analysis in several European case-control sample sets, with a total of 4,739 cases and 45,549 controls. The T allele of rs798766 on 4p16.3 was found to associate with UBC (odds ratio = 1.24, P = 9.9 x 10(-12)). rs798766 is located in an intron of TACC3, 70 kb from FGFR3, which often harbors activating somatic mutations in low-grade, noninvasive UBC. Notably, rs798766[T] shows stronger association with low-grade and low-stage UBC than with more aggressive forms of the disease and is associated with higher risk of recurrence in low-grade stage Ta tumors. The frequency of rs798766[T] is higher in Ta tumors that carry an activating mutation in FGFR3 than in Ta tumors with wild-type FGFR3. Our results show a link between germline variants, somatic mutations of FGFR3 and risk of UBC

AB - Previously, we reported germline DNA variants associated with risk of urinary bladder cancer (UBC) in Dutch and Icelandic subjects. Here we expanded the Icelandic sample set and tested the top 20 markers from the combined analysis in several European case-control sample sets, with a total of 4,739 cases and 45,549 controls. The T allele of rs798766 on 4p16.3 was found to associate with UBC (odds ratio = 1.24, P = 9.9 x 10(-12)). rs798766 is located in an intron of TACC3, 70 kb from FGFR3, which often harbors activating somatic mutations in low-grade, noninvasive UBC. Notably, rs798766[T] shows stronger association with low-grade and low-stage UBC than with more aggressive forms of the disease and is associated with higher risk of recurrence in low-grade stage Ta tumors. The frequency of rs798766[T] is higher in Ta tumors that carry an activating mutation in FGFR3 than in Ta tumors with wild-type FGFR3. Our results show a link between germline variants, somatic mutations of FGFR3 and risk of UBC

KW - FGFR3

KW - bladder cancer

KW - genome-wide association study

KW - FGFR3

KW - bladder cancer

KW - genome-wide association study

UR - https://iris.uniupo.it/handle/11579/223148

U2 - 10.1038/ng.558

DO - 10.1038/ng.558

M3 - Article

SN - 1061-4036

VL - 42

SP - 415

EP - 419

JO - Nature Genetics

JF - Nature Genetics

IS - 5

ER -

A sequence variant at 4p16.3 confers susceptibility to urinary bladder cancer

Abstract

Keywords

OSS delle Nazioni Unite

Accesso al documento

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