The 19q12 bladder cancer GWAS signal: association with cyclin E function and aggressive disease

Fu, Y. P.; Kohaar, I.; Moore, L. E.; Lenz, P.; Figueroa, J. D.; Tang, W.; Porter-Gill, P.; Chatterjee, N.; Scott-Johnson, A.; Garcia-Closas, M.; Muchmore, B.; Baris, D.; Paquin, A.; Ylaya, K.; Schwenn, M.; Apolo, A. B.; Karagas, M. R.; Tarway, M.; Johnson, A.; Mumy, A.; Schned, A.; Guedez, L.; Jones, M. A.; Kida, M.; Hosain, G. M.; Malats, N.; Kogevinas, M.; Tardon, A.; Serra, C.; Carrato, A.; Garcia-Closas, R.; Lloreta, J.; Wu, X.; Purdue, M.; Andriole, G. L.; Grubb, R. L.; Black, A.; Landi, M. T.; Caporaso, N. E.; Vineis, P.; Siddiq, A.; Bueno-de-Mesquita, H. B.; Trichopoulos, D.; Ljungberg, B.; Severi, G.; Weiderpass, E.; Krogh, V.; Dorronsoro, M.; Travis, R. C.; Tjønneland, A.; Brennan, P.; Chang-Claude, J.; Riboli, E.; Prescott, J.; Chen, C.; De Vivo, I.; Govannucci, E.; Hunter, D.; Kraft, P.; Lindstrom, S.; Gapstur, S. M.; Jacobs, E. J.; Diver, W. R.; Albanes, D.; Weinstein, S. J.; Virtamo, J.; Kooperberg, C.; Hohensee, C.; Rodabough, R. J.; Cortessis, V. K.; Conti, D. V.; Gago Dominguez, Manuela; Stern, M. C.; Pike, M. C.; Van Den Berg, D.; Yuan, J. M.; Haiman, C. A.; Cussenot, O.; Cancel-Tassin, G.; Roupret, M.; Comperat, E.; Porru, S.; Carta, A.; Pavanello, S.; Arici, C.; Mastrangelo, G.; Grossman, H. B.; Wang, Z.; Deng, X.; Chung, C. C.; Hutchinson, A.; Burdette, L.; Wheeler, W.; Fraumeni, J.; Chanock, S. J.; Hewitt, S. M.; Silverman, D. T.; Rothman, N.; Prokunina-Olsson, L.

The 19q12 bladder cancer GWAS signal: association with cyclin E function and aggressive disease

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...

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Autores:	Fu, Y. P., Kohaar, I., Moore, L. E., Lenz, P., Figueroa, J. D., Tang, W., Porter-Gill, P., Chatterjee, N., Scott-Johnson, A., Garcia-Closas, M., Muchmore, B., Baris, D., Paquin, A., Ylaya, K., Schwenn, M., Apolo, A. B., Karagas, M. R., Tarway, M., Johnson, A., Mumy, A., Schned, A., Guedez, L., Jones, M. A., Kida, M., Hosain, G. M., Malats, N., Kogevinas, M., Tardon, A., Serra, C., Carrato, A., Garcia-Closas, R., Lloreta, J., Wu, X., Purdue, M., Andriole, G. L., Grubb, R. L., Black, A., Landi, M. T., Caporaso, N. E., Vineis, P., Siddiq, A., Bueno-de-Mesquita, H. B., Trichopoulos, D., Ljungberg, B., Severi, G., Weiderpass, E., Krogh, V., Dorronsoro, M., Travis, R. C., Tjønneland, A., Brennan, P., Chang-Claude, J., Riboli, E., Prescott, J., Chen, C., De Vivo, I., Govannucci, E., Hunter, D., Kraft, P., Lindstrom, S., Gapstur, S. M., Jacobs, E. J., Diver, W. R., Albanes, D., Weinstein, S. J., Virtamo, J., Kooperberg, C., Hohensee, C., Rodabough, R. J., Cortessis, V. K., Conti, D. V., Gago Dominguez, Manuela, Stern, M. C., Pike, M. C., Van Den Berg, D., Yuan, J. M., Haiman, C. A., Cussenot, O., Cancel-Tassin, G., Roupret, M., Comperat, E., Porru, S., Carta, A., Pavanello, S., Arici, C., Mastrangelo, G., Grossman, H. B., Wang, Z., Deng, X., Chung, C. C., Hutchinson, A., Burdette, L., Wheeler, W., Fraumeni, J., Chanock, S. J., Hewitt, S. M., Silverman, D. T., Rothman, N., Prokunina-Olsson, L.
Tipo de recurso:	artículo
Fecha de publicación:	2014
País:	España
Institución:	Servizo Galego de Saúde (SERGAS)
Repositorio:	RUNA. Repositorio da Consellería de Sanidade e Sergas
OAI Identifier:	oai:runa.sergas.gal:20.500.11940/4605
Acceso en línea:	http://hdl.handle.net/20.500.11940/4605
Access Level:	acceso abierto
Palabra clave:	Case-Control Studies Chromosomes, Human, Pair 19 Cyclin E Gene Expression Gene Frequency Genome-Wide Association Study Haplotypes HeLa Cells Humans Oncogene Proteins Polymorphism, Single Nucleotide Urinary Bladder Urinary Bladder Neoplasms

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spelling	The 19q12 bladder cancer GWAS signal: association with cyclin E function and aggressive diseaseFu, Y. P.Kohaar, I.Moore, L. E.Lenz, P.Figueroa, J. D.Tang, W.Porter-Gill, P.Chatterjee, N.Scott-Johnson, A.Garcia-Closas, M.Muchmore, B.Baris, D.Paquin, A.Ylaya, K.Schwenn, M.Apolo, A. B.Karagas, M. R.Tarway, M.Johnson, A.Mumy, A.Schned, A.Guedez, L.Jones, M. A.Kida, M.Hosain, G. M.Malats, N.Kogevinas, M.Tardon, A.Serra, C.Carrato, A.Garcia-Closas, R.Lloreta, J.Wu, X.Purdue, M.Andriole, G. L.Grubb, R. L.Black, A.Landi, M. T.Caporaso, N. E.Vineis, P.Siddiq, A.Bueno-de-Mesquita, H. B.Trichopoulos, D.Ljungberg, B.Severi, G.Weiderpass, E.Krogh, V.Dorronsoro, M.Travis, R. C.Tjønneland, A.Brennan, P.Chang-Claude, J.Riboli, E.Prescott, J.Chen, C.De Vivo, I.Govannucci, E.Hunter, D.Kraft, P.Lindstrom, S.Gapstur, S. M.Jacobs, E. J.Diver, W. R.Albanes, D.Weinstein, S. J.Virtamo, J.Kooperberg, C.Hohensee, C.Rodabough, R. J.Cortessis, V. K.Conti, D. V.Gago Dominguez, ManuelaStern, M. C.Pike, M. C.Van Den Berg, D.Yuan, J. M.Haiman, C. A.Cussenot, O.Cancel-Tassin, G.Roupret, M.Comperat, E.Porru, S.Carta, A.Pavanello, S.Arici, C.Mastrangelo, G.Grossman, H. B.Wang, Z.Deng, X.Chung, C. C.Hutchinson, A.Burdette, L.Wheeler, W.Fraumeni, J.Chanock, S. J.Hewitt, S. M.Silverman, D. T.Rothman, N.Prokunina-Olsson, L.Case-Control StudiesChromosomes, Human, Pair 19Cyclin EGene ExpressionGene FrequencyGenome-Wide Association StudyHaplotypesHeLa CellsHumansOncogene ProteinsPolymorphism, Single NucleotideUrinary BladderUrinary Bladder NeoplasmsA 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.2014info:eu-repo/semantics/articlehttp://hdl.handle.net/20.500.11940/4605reponame:RUNA. Repositorio da Consellería de Sanidade e Sergasinstname:Servizo Galego de Saúde (SERGAS)Inglésinfo:eu-repo/semantics/openAccessoai:runa.sergas.gal:20.500.11940/46052026-06-12T08:40:47Z
dc.title.none.fl_str_mv	The 19q12 bladder cancer GWAS signal: association with cyclin E function and aggressive disease
title	The 19q12 bladder cancer GWAS signal: association with cyclin E function and aggressive disease
spellingShingle	The 19q12 bladder cancer GWAS signal: association with cyclin E function and aggressive disease Fu, Y. P. Case-Control Studies Chromosomes, Human, Pair 19 Cyclin E Gene Expression Gene Frequency Genome-Wide Association Study Haplotypes HeLa Cells Humans Oncogene Proteins Polymorphism, Single Nucleotide Urinary Bladder Urinary Bladder Neoplasms
title_short	The 19q12 bladder cancer GWAS signal: association with cyclin E function and aggressive disease
title_full	The 19q12 bladder cancer GWAS signal: association with cyclin E function and aggressive disease
title_fullStr	The 19q12 bladder cancer GWAS signal: association with cyclin E function and aggressive disease
title_full_unstemmed	The 19q12 bladder cancer GWAS signal: association with cyclin E function and aggressive disease
title_sort	The 19q12 bladder cancer GWAS signal: association with cyclin E function and aggressive disease
dc.creator.none.fl_str_mv	Fu, Y. P. Kohaar, I. Moore, L. E. Lenz, P. Figueroa, J. D. Tang, W. Porter-Gill, P. Chatterjee, N. Scott-Johnson, A. Garcia-Closas, M. Muchmore, B. Baris, D. Paquin, A. Ylaya, K. Schwenn, M. Apolo, A. B. Karagas, M. R. Tarway, M. Johnson, A. Mumy, A. Schned, A. Guedez, L. Jones, M. A. Kida, M. Hosain, G. M. Malats, N. Kogevinas, M. Tardon, A. Serra, C. Carrato, A. Garcia-Closas, R. Lloreta, J. Wu, X. Purdue, M. Andriole, G. L. Grubb, R. L. Black, A. Landi, M. T. Caporaso, N. E. Vineis, P. Siddiq, A. Bueno-de-Mesquita, H. B. Trichopoulos, D. Ljungberg, B. Severi, G. Weiderpass, E. Krogh, V. Dorronsoro, M. Travis, R. C. Tjønneland, A. Brennan, P. Chang-Claude, J. Riboli, E. Prescott, J. Chen, C. De Vivo, I. Govannucci, E. Hunter, D. Kraft, P. Lindstrom, S. Gapstur, S. M. Jacobs, E. J. Diver, W. R. Albanes, D. Weinstein, S. J. Virtamo, J. Kooperberg, C. Hohensee, C. Rodabough, R. J. Cortessis, V. K. Conti, D. V. Gago Dominguez, Manuela Stern, M. C. Pike, M. C. Van Den Berg, D. Yuan, J. M. Haiman, C. A. Cussenot, O. Cancel-Tassin, G. Roupret, M. Comperat, E. Porru, S. Carta, A. Pavanello, S. Arici, C. Mastrangelo, G. Grossman, H. B. Wang, Z. Deng, X. Chung, C. C. Hutchinson, A. Burdette, L. Wheeler, W. Fraumeni, J. Chanock, S. J. Hewitt, S. M. Silverman, D. T. Rothman, N. Prokunina-Olsson, L.
author	Fu, Y. P.
author_facet	Fu, Y. P. Kohaar, I. Moore, L. E. Lenz, P. Figueroa, J. D. Tang, W. Porter-Gill, P. Chatterjee, N. Scott-Johnson, A. Garcia-Closas, M. Muchmore, B. Baris, D. Paquin, A. Ylaya, K. Schwenn, M. Apolo, A. B. Karagas, M. R. Tarway, M. Johnson, A. Mumy, A. Schned, A. Guedez, L. Jones, M. A. Kida, M. Hosain, G. M. Malats, N. Kogevinas, M. Tardon, A. Serra, C. Carrato, A. Garcia-Closas, R. Lloreta, J. Wu, X. Purdue, M. Andriole, G. L. Grubb, R. L. Black, A. Landi, M. T. Caporaso, N. E. Vineis, P. Siddiq, A. Bueno-de-Mesquita, H. B. Trichopoulos, D. Ljungberg, B. Severi, G. Weiderpass, E. Krogh, V. Dorronsoro, M. Travis, R. C. Tjønneland, A. Brennan, P. Chang-Claude, J. Riboli, E. Prescott, J. Chen, C. De Vivo, I. Govannucci, E. Hunter, D. Kraft, P. Lindstrom, S. Gapstur, S. M. Jacobs, E. J. Diver, W. R. Albanes, D. Weinstein, S. J. Virtamo, J. Kooperberg, C. Hohensee, C. Rodabough, R. J. Cortessis, V. K. Conti, D. V. Gago Dominguez, Manuela Stern, M. C. Pike, M. C. Van Den Berg, D. Yuan, J. M. Haiman, C. A. Cussenot, O. Cancel-Tassin, G. Roupret, M. Comperat, E. Porru, S. Carta, A. Pavanello, S. Arici, C. Mastrangelo, G. Grossman, H. B. Wang, Z. Deng, X. Chung, C. C. Hutchinson, A. Burdette, L. Wheeler, W. Fraumeni, J. Chanock, S. J. Hewitt, S. M. Silverman, D. T. Rothman, N. Prokunina-Olsson, L.
author_role	author
author2	Kohaar, I. Moore, L. E. Lenz, P. Figueroa, J. D. Tang, W. Porter-Gill, P. Chatterjee, N. Scott-Johnson, A. Garcia-Closas, M. Muchmore, B. Baris, D. Paquin, A. Ylaya, K. Schwenn, M. Apolo, A. B. Karagas, M. R. Tarway, M. Johnson, A. Mumy, A. Schned, A. Guedez, L. Jones, M. A. Kida, M. Hosain, G. M. Malats, N. Kogevinas, M. Tardon, A. Serra, C. Carrato, A. Garcia-Closas, R. Lloreta, J. Wu, X. Purdue, M. Andriole, G. L. Grubb, R. L. Black, A. Landi, M. T. Caporaso, N. E. Vineis, P. Siddiq, A. Bueno-de-Mesquita, H. B. Trichopoulos, D. Ljungberg, B. Severi, G. Weiderpass, E. Krogh, V. Dorronsoro, M. Travis, R. C. Tjønneland, A. Brennan, P. Chang-Claude, J. Riboli, E. Prescott, J. Chen, C. De Vivo, I. Govannucci, E. Hunter, D. Kraft, P. Lindstrom, S. Gapstur, S. M. Jacobs, E. J. Diver, W. R. Albanes, D. Weinstein, S. J. Virtamo, J. Kooperberg, C. Hohensee, C. Rodabough, R. J. Cortessis, V. K. Conti, D. V. Gago Dominguez, Manuela Stern, M. C. Pike, M. C. Van Den Berg, D. Yuan, J. M. Haiman, C. A. Cussenot, O. Cancel-Tassin, G. Roupret, M. Comperat, E. Porru, S. Carta, A. Pavanello, S. Arici, C. Mastrangelo, G. Grossman, H. B. Wang, Z. Deng, X. Chung, C. C. Hutchinson, A. Burdette, L. Wheeler, W. Fraumeni, J. Chanock, S. J. Hewitt, S. M. Silverman, D. T. Rothman, N. Prokunina-Olsson, L.
author2_role	author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author
dc.subject.none.fl_str_mv	Case-Control Studies Chromosomes, Human, Pair 19 Cyclin E Gene Expression Gene Frequency Genome-Wide Association Study Haplotypes HeLa Cells Humans Oncogene Proteins Polymorphism, Single Nucleotide Urinary Bladder Urinary Bladder Neoplasms
topic	Case-Control Studies Chromosomes, Human, Pair 19 Cyclin E Gene Expression Gene Frequency Genome-Wide Association Study Haplotypes HeLa Cells Humans Oncogene Proteins Polymorphism, Single Nucleotide Urinary Bladder Urinary Bladder Neoplasms
description	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.
publishDate	2014
dc.date.none.fl_str_mv	2014
dc.type.none.fl_str_mv	info:eu-repo/semantics/article
format	article
dc.identifier.none.fl_str_mv	http://hdl.handle.net/20.500.11940/4605
url	http://hdl.handle.net/20.500.11940/4605
dc.language.none.fl_str_mv	Inglés
language_invalid_str_mv	Inglés
dc.rights.none.fl_str_mv	info:eu-repo/semantics/openAccess
eu_rights_str_mv	openAccess
dc.source.none.fl_str_mv	reponame:RUNA. Repositorio da Consellería de Sanidade e Sergas instname:Servizo Galego de Saúde (SERGAS)
instname_str	Servizo Galego de Saúde (SERGAS)
reponame_str	RUNA. Repositorio da Consellería de Sanidade e Sergas
collection	RUNA. Repositorio da Consellería de Sanidade e Sergas
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The 19q12 bladder cancer GWAS signal: association with cyclin E function and aggressive disease

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