The 19q12 Bladder Cancer GWAS Signal: Association with Cyclin E Function and Aggressive Disease

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Fältnamn	Indikatorer	Metadata
000		07224naa a2201513 4500
001		oai:DiVA.org:umu-96817
003		SwePub
008		141203s2014 \| \|\|\|\|\|\|\|\|\|\|\|000 \|\|eng\|
009		oai:prod.swepub.kib.ki.se:129986425
024	7	a https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-968172 URI
024	7	a https://doi.org/10.1158/0008-5472.CAN-14-15312 DOI
024	7	a http://kipublications.ki.se/Default.aspx?queryparsed=id:1299864252 URI
040		a (SwePub)umud (SwePub)ki
041		a engb eng
042		9 SwePub
072	7	a ref2 swepub-contenttype
072	7	a art2 swepub-publicationtype
100	1	a Fu, Yi-Ping4 aut
245	1 0	a The 19q12 Bladder Cancer GWAS Signal :b Association with Cyclin E Function and Aggressive Disease
264	1	c 2014
338		a print2 rdacarrier
520		a A genome-wide association study (GWAS) of bladder cancer identified a genetic marker rs8102137 within the 19q12 region as a novel susceptibility variant. This marker is located upstream of the CCNE1 gene, which encodes cyclin E, a cell-cycle protein. We performed genetic fine-mapping analysis of the CCNE1 region using data from two bladder cancer GWAS (5,942 cases and 10,857 controls). We found that the original GWAS marker rs8102137 represents a group of 47 linked SNPs (with r(2) >= 0.7) associated with increased bladder cancer risk. From this group, we selected a functional promoter variant rs7257330, which showed strong allele-specific binding of nuclear proteins in several cell lines. In both GWASs, rs7257330 was associated only with aggressive bladder cancer, with a combined per-allele OR = 1.18 [95% confidence interval (CI), 1.09-1.27, P = 4.67 x 10(-5)] versus OR = 1.01 (95% CI, 0.93-1.10, P = 0.79) for nonaggressive disease, with P = 0.0015 for case-only analysis. Cyclin E protein expression analyzed in 265 bladder tumors was increased in aggressive tumors (P = 0.013) and, independently, with each rs7257330-A risk allele (P-trend = 0.024). Overexpression of recombinant cyclin E in cell lines caused significant acceleration of cell cycle. In conclusion, we defined the 19q12 signal as the first GWAS signal specific for aggressive bladder cancer. Molecular mechanisms of this genetic association may be related to cyclin E overexpression and alteration of cell cycle in carriers of CCNE1 risk variants. In combination with established bladder cancer risk factors and other somatic and germline genetic markers, the CCNE1 variants could be useful for inclusion into bladder cancer risk prediction models.
650	7	a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Cancer och onkologi0 (SwePub)302032 hsv//swe
650	7	a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Cancer and Oncology0 (SwePub)302032 hsv//eng
650	7	a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Urologi och njurmedicin0 (SwePub)302142 hsv//swe
650	7	a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Urology and Nephrology0 (SwePub)302142 hsv//eng
700	1	a Kohaar, Indu4 aut
700	1	a Moore, Lee E.4 aut
700	1	a Lenz, Petra4 aut
700	1	a Figueroa, Jonine D.4 aut
700	1	a Tang, Wei4 aut
700	1	a Porter-Gill, Patricia4 aut
700	1	a Chatterjee, Nilanjan4 aut
700	1	a Scott-Johnson, Alexandra4 aut
700	1	a Garcia-Closas, Montserrat4 aut
700	1	a Muchmore, Brian4 aut
700	1	a Baris, Dalsu4 aut
700	1	a Paquin, Ashley4 aut
700	1	a Ylaya, Kris4 aut
700	1	a Schwenn, Molly4 aut
700	1	a Apolo, Andrea B.4 aut
700	1	a Karagas, Margaret R.4 aut
700	1	a Tarway, McAnthony4 aut
700	1	a Johnson, Alison4 aut
700	1	a Mumy, Adam4 aut
700	1	a Schned, Alan4 aut
700	1	a Guedez, Liliana4 aut
700	1	a Jones, Michael A.4 aut
700	1	a Kida, Masatoshi4 aut
700	1	a Hosain, G. M. Monawar4 aut
700	1	a Malats, Nuria4 aut
700	1	a Kogevinas, Manolis4 aut
700	1	a Tardon, Adonina4 aut
700	1	a Serra, Consol4 aut
700	1	a Carrato, Alfredo4 aut
700	1	a Garcia-Closas, Reina4 aut
700	1	a Lloreta, Josep4 aut
700	1	a Wu, Xifeng4 aut
700	1	a Purdue, Mark4 aut
700	1	a Andriole, Gerald L., Jr.4 aut
700	1	a Grubb, Robert L., III4 aut
700	1	a Black, Amanda4 aut
700	1	a Landi, Maria T.4 aut
700	1	a Caporaso, Neil E.4 aut
700	1	a Vineis, Paolo4 aut
700	1	a Siddiq, Afshan4 aut
700	1	a Bueno-de-Mesquita, H. Bas4 aut
700	1	a Trichopoulos, Dimitrios4 aut
700	1	a Ljungberg, Börjeu Umeå universitet,Urologi och andrologi,Njurcancer4 aut0 (Swepub:umu)bolj0001
700	1	a Severi, Gianluca4 aut
700	1	a Weiderpass, Elisabeteu Karolinska Institutet4 aut
700	1	a Krogh, Vittorio4 aut
700	1	a Dorronsoro, Miren4 aut
700	1	a Travis, Ruth C.4 aut
700	1	a Tjonneland, Anne4 aut
700	1	a Brennan, Paul4 aut
700	1	a Chang-Claude, Jenny4 aut
700	1	a Riboli, Elio4 aut
700	1	a Prescott, Jennifer4 aut
700	1	a Chen, Constance4 aut
700	1	a De Vivo, Immaculata4 aut
700	1	a Govannucci, Edward4 aut
700	1	a Hunter, David4 aut
700	1	a Kraft, Peter4 aut
700	1	a Lindstrom, Sara4 aut
700	1	a Gapstur, Susan M.4 aut
700	1	a Jacobs, Eric J.4 aut
700	1	a Diver, W. Ryan4 aut
700	1	a Albanes, Demetrius4 aut
700	1	a Weinstein, Stephanie J.4 aut
700	1	a Virtamo, Jarmo4 aut
700	1	a Kooperberg, Charles4 aut
700	1	a Hohensee, Chancellor4 aut
700	1	a Rodabough, Rebecca J.4 aut
700	1	a Cortessis, Victoria K.4 aut
700	1	a Conti, David V.4 aut
700	1	a Gago-Dominguez, Manuela4 aut
700	1	a Stern, Mariana C.4 aut
700	1	a Pike, Malcolm C.4 aut
700	1	a Van Den Berg, David4 aut
700	1	a Yuan, Jian-Min4 aut
700	1	a Haiman, Christopher A.4 aut
700	1	a Cussenot, Olivier4 aut
700	1	a Cancel-Tassin, Geraldine4 aut
700	1	a Roupret, Morgan4 aut
700	1	a Comperat, Eva4 aut
700	1	a Porru, Stefano4 aut
700	1	a Carta, Angela4 aut
700	1	a Pavanello, Sofia4 aut
700	1	a Arici, Cecilia4 aut
700	1	a Mastrangelo, Giuseppe4 aut
700	1	a Grossman, H. Barton4 aut
700	1	a Wang, Zhaoming4 aut
700	1	a Deng, Xiang4 aut
700	1	a Chung, Charles C.4 aut
700	1	a Hutchinson, Amy4 aut
700	1	a Burdette, Laurie4 aut
700	1	a Wheeler, William4 aut
700	1	a Fraumeni, Joseph, Jr.4 aut
700	1	a Chanock, Stephen J.4 aut
700	1	a Hewitt, Stephen M.4 aut
700	1	a Silverman, Debra T.4 aut
700	1	a Rothman, Nathaniel4 aut
700	1	a Prokunina-Olsson, Ludmila4 aut
710	2	a Umeå universitetb Urologi och andrologi4 org
773	0	t Cancer Researchg 74:20, s. 5808-5818q 74:20<5808-5818x 0008-5472x 1538-7445
856	4 8	u https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-96817
856	4 8	u https://doi.org/10.1158/0008-5472.CAN-14-1531
856	4 8	u http://kipublications.ki.se/Default.aspx?queryparsed=id:129986425

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Av författaren/redakt...: Fu, Yi-Ping; Kohaar, Indu; Moore, Lee E.; Lenz, Petra; Figueroa, Jonine ...; Tang, Wei; visa fler...; Porter-Gill, Pat ...; Chatterjee, Nila ...; Scott-Johnson, A ...; Garcia-Closas, M ...; Muchmore, Brian; Baris, Dalsu; Paquin, Ashley; Ylaya, Kris; Schwenn, Molly; Apolo, Andrea B.; Karagas, Margare ...; Tarway, McAnthon ...; Johnson, Alison; Mumy, Adam; Schned, Alan; Guedez, Liliana; Jones, Michael A ...; Kida, Masatoshi; Hosain, G. M. Mo ...; Malats, Nuria; Kogevinas, Manol ...; Tardon, Adonina; Serra, Consol; Carrato, Alfredo; Garcia-Closas, R ...; Lloreta, Josep; Wu, Xifeng; Purdue, Mark; Andriole, Gerald ...; Grubb, Robert L. ...; Black, Amanda; Landi, Maria T.; Caporaso, Neil E ...; Vineis, Paolo; Siddiq, Afshan; Bueno-de-Mesquit ...; Trichopoulos, Di ...; Ljungberg, Börje; Severi, Gianluca; Weiderpass, Elis ...; Krogh, Vittorio; Dorronsoro, Mire ...; Travis, Ruth C.; Tjonneland, Anne; Brennan, Paul; Chang-Claude, Je ...; Riboli, Elio; Prescott, Jennif ...; Chen, Constance; De Vivo, Immacul ...; Govannucci, Edwa ...; Hunter, David; Kraft, Peter; Lindstrom, Sara; Gapstur, Susan M ...; Jacobs, Eric J.; Diver, W. Ryan; Albanes, Demetri ...; Weinstein, Steph ...; Virtamo, Jarmo; Kooperberg, Char ...; Hohensee, Chance ...; Rodabough, Rebec ...; Cortessis, Victo ...; Conti, David V.; Gago-Dominguez, ...; Stern, Mariana C ...; Pike, Malcolm C.; Van Den Berg, Da ...; Yuan, Jian-Min; Haiman, Christop ...; Cussenot, Olivie ...; Cancel-Tassin, G ...; Roupret, Morgan; Comperat, Eva; Porru, Stefano; Carta, Angela; Pavanello, Sofia; Arici, Cecilia; Mastrangelo, Giu ...; Grossman, H. Bar ...; Wang, Zhaoming; Deng, Xiang; Chung, Charles C ...; Hutchinson, Amy; Burdette, Laurie; Wheeler, William; Fraumeni, Joseph ...; Chanock, Stephen ...; Hewitt, Stephen ...; Silverman, Debra ...; Rothman, Nathani ...; Prokunina-Olsson ...; visa färre...

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MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Klinisk medicin; och Cancer och onkol ...

MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Klinisk medicin; och Urologi och njur ...

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Av lärosätet: Umeå universitet; Karolinska Institutet

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