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

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

doi:10.1038/ng.558

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

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

genome-wide association study
bladder cancer
FGFR3

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

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

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

}

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

AU - Sulem, P

AU - Besenbacher, S

AU - Vermeulen, SH

AU - Sigurdsson, A

AU - Thorleifsson, G

AU - Gudbjartsson, DF

AU - Stacey, SN

AU - Gudmundsson, J

AU - Zanon, C

AU - Kostic, J

AU - Masson, G

AU - Bjarnason, H

AU - Palsson, ST

AU - Skarphedinsson, OB

AU - Gudjonsson, SA

AU - Witjes, JA

AU - Grotenhuis, AJ

AU - Verhaegh, GW

AU - Bishop, DT

AU - Sak, SC

AU - Choudhury, A

AU - Elliott, F

AU - Barrett, JH

AU - Hurst, CD

AU - de, Verdier PJ

AU - Ryk, C

AU - Rudnai, P

AU - Gurzau, E

AU - Koppova, K

AU - Paolo, VINEIS

AU - POLIDORO, Silvia

AU - Simonetta, GUARRERA

AU - SACERDOTE, Carlotta

AU - Campagna, M

AU - Placidi, D

AU - Arici, C

AU - Zeegers, MP

AU - Kellen, E

AU - Gutierrez, BS

AU - Sanz, Velez JI

AU - Sanchez, Zalabardo M

AU - Valdivia, G

AU - Garcia, Prats MD

AU - Hengstler, JG

AU - Blaszkewicz, M

AU - Dietrich, H

AU - Ophoff, RA

AU - van, den Berg LH

AU - Alexiusdottir, K

AU - Kristjansson, K

AU - Geirsson, G

AU - Nikulasson, S

AU - Petursdottir, V

AU - Kong, A

AU - Thorgeirsson, T

AU - Mungan, NA

AU - Lindblom, A

AU - van, Es MA

AU - Porru, S

AU - Buntinx, F

AU - Golka, K

AU - Mayordomo, JI

AU - Kumar, R

AU - Giuseppe, MATULLO

AU - Steineck, G

AU - Kiltie, AE

AU - Aben, KK

AU - Jonsson, E

AU - Thorsteinsdottir, U

AU - Knowles, MA

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 - genome-wide association study

KW - bladder cancer

KW - FGFR3

KW - genome-wide association study

KW - bladder cancer

KW - FGFR3

UR - https://iris.uniupo.it/handle/null

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

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