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

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

Fu, Yi-Ping (author)

Kohaar, Indu (author)

Moore, Lee E. (author)

Lenz, Petra (author)

Figueroa, Jonine D. (author)

Tang, Wei (author)

Porter-Gill, Patricia (author)

Chatterjee, Nilanjan (author)

Scott-Johnson, Alexandra (author)

Garcia-Closas, Montserrat (author)

Muchmore, Brian (author)

Baris, Dalsu (author)

Paquin, Ashley (author)

Ylaya, Kris (author)

Schwenn, Molly (author)

Apolo, Andrea B. (author)

Karagas, Margaret R. (author)

Tarway, McAnthony (author)

Johnson, Alison (author)

Mumy, Adam (author)

Schned, Alan (author)

Guedez, Liliana (author)

Jones, Michael A. (author)

Kida, Masatoshi (author)

Hosain, G. M. Monawar (author)

Malats, Nuria (author)

Kogevinas, Manolis (author)

Tardon, Adonina (author)

Serra, Consol (author)

Carrato, Alfredo (author)

Garcia-Closas, Reina (author)

Lloreta, Josep (author)

Wu, Xifeng (author)

Purdue, Mark (author)

Andriole, Gerald L., Jr. (author)

Grubb, Robert L., III (author)

Black, Amanda (author)

Landi, Maria T. (author)

Caporaso, Neil E. (author)

Vineis, Paolo (author)

Siddiq, Afshan (author)

Bueno-de-Mesquita, H. Bas (author)

Trichopoulos, Dimitrios (author)

Ljungberg, Börje (author): Umeå universitet,Urologi och andrologi,Njurcancer

Severi, Gianluca (author)

Weiderpass, Elisabete (author): Karolinska Institutet

Krogh, Vittorio (author)

Dorronsoro, Miren (author)

Travis, Ruth C. (author)

Tjonneland, Anne (author)

Brennan, Paul (author)

Chang-Claude, Jenny (author)

Riboli, Elio (author)

Prescott, Jennifer (author)

Chen, Constance (author)

De Vivo, Immaculata (author)

Govannucci, Edward (author)

Hunter, David (author)

Kraft, Peter (author)

Lindstrom, Sara (author)

Gapstur, Susan M. (author)

Jacobs, Eric J. (author)

Diver, W. Ryan (author)

Albanes, Demetrius (author)

Weinstein, Stephanie J. (author)

Virtamo, Jarmo (author)

Kooperberg, Charles (author)

Hohensee, Chancellor (author)

Rodabough, Rebecca J. (author)

Cortessis, Victoria K. (author)

Conti, David V. (author)

Gago-Dominguez, Manuela (author)

Stern, Mariana C. (author)

Pike, Malcolm C. (author)

Van Den Berg, David (author)

Yuan, Jian-Min (author)

Haiman, Christopher A. (author)

Cussenot, Olivier (author)

Cancel-Tassin, Geraldine (author)

Roupret, Morgan (author)

Comperat, Eva (author)

Porru, Stefano (author)

Carta, Angela (author)

Pavanello, Sofia (author)

Arici, Cecilia (author)

Mastrangelo, Giuseppe (author)

Grossman, H. Barton (author)

Wang, Zhaoming (author)

Deng, Xiang (author)

Chung, Charles C. (author)

Hutchinson, Amy (author)

Burdette, Laurie (author)

Wheeler, William (author)

Fraumeni, Joseph, Jr. (author)

Chanock, Stephen J. (author)

Hewitt, Stephen M. (author)

Silverman, Debra T. (author)

Rothman, Nathaniel (author)

Prokunina-Olsson, Ludmila (author)

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(creator_code:org_t)

2014
2014
English.
In: Cancer Research. - 0008-5472 .- 1538-7445. ; 74:20, s. 5808-5818

Related links:: https://urn.kb.se/re...; show more...; https://doi.org/10.1...; http://kipublication...; show less...

Journal article (peer-reviewed)

Abstract Subject headings

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.

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By the author/editor: Fu, Yi-Ping; Kohaar, Indu; Moore, Lee E.; Lenz, Petra; Figueroa, Jonine ...; Tang, Wei; show more...; 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 ...; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Cancer and Oncol ...

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Urology and Neph ...

Articles in the publication: Cancer Research

By the university: Umeå University; Karolinska Institutet

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

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