Abstract
While interplay between BRCA1 and AURKA-RHAMM-TPX2-TUBG1 regulates mammary epithelial polarization, common genetic variation in HMMR (gene product RHAMM) may be associated with risk of breast cancer in BRCA1 mutation carriers. Following on these observations, we further assessed the link between the AURKA-HMMR-TPX2-TUBG1 functional module and risk of breast cancer in BRCA1 or BRCA2 mutation carriers. Forty-one single nucleotide polymorphisms (SNPs) were genotyped in 15,252 BRCA1 and 8,211 BRCA2 mutation carriers and subsequently analyzed using a retrospective likelihood approach. The association of HMMR rs299290 with breast cancer risk in BRCA1 mutation carriers was confirmed: per-allele hazard ratio (HR) = 1.10, 95% confidence interval (CI) 1.04 - 1.15, p = 1.9 × 10-4 (false discovery rate (FDR)-adjusted p = 0.043). Variation in CSTF1, located next to AURKA, was also found to be associated with breast cancer risk in BRCA2 mutation carriers: rs2426618 per-allele HR = 1.10, 95% CI 1.03 - 1.16, p = 0.005 (FDR-adjusted p = 0.045). Assessment of pairwise interactions provided suggestions (FDR-adjusted pinteraction values > 0.05) for deviations from the multiplicative model for rs299290 and CSTF1 rs6064391, and rs299290 and TUBG1 rs11649877 in both BRCA1 and BRCA2 mutation carriers. Following these suggestions, the expression of HMMR and AURKA or TUBG1 in sporadic breast tumors was found to potentially interact, influencing patients' survival. Together, the results of this study support the hypothesis of a causative link between altered function of AURKA-HMMR-TPX2-TUBG1 and breast carcinogenesis in BRCA1/2 mutation carriers.
| Original language | English |
|---|---|
| Article number | 120020 |
| Journal | PLoS One |
| Volume | 10 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Apr 1 2015 |
ASJC Scopus subject areas
- Agricultural and Biological Sciences(all)
- Biochemistry, Genetics and Molecular Biology(all)
- Medicine(all)
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Assessing associations between the AURKAHMMR-TPX2-TUBG1 functional module and breast cancer risk in BRCA1/2 mutation carriers. / Blanco, Ignacio; Kuchenbaecker, Karoline; Cuadras, Daniel; Wang, Xianshu; Barrowdale, Daniel; De Garibay, Gorka Ruiz; Librado, Pablo; Sánchez-Gracia, Alejandro; Rozas, Julio; Bonifaci, Núria; McGuffog, Lesley; Pankratz, Vernon S.; Islam, Abul; Mateo, Francesca; Berenguer, Antoni; Petit, Anna; Català, Isabel; Brunet, Joan; Feliubadaló, Lidia; Tornero, Eva; Benítez, Javier; Osorio, Ana; Teresa, Ramón; Teresa, Cajal; Nevanlinna, Heli; Aittomäki, Kristiina; Arun, Banu K.; Toland, Amanda E.; Karlan, Beth Y.; Walsh, Christine; Lester, Jenny; Greene, Mark H.; Mai, Phuong L.; Nussbaum, Robert L.; Andrulis, Irene L.; Domchek, Susan M.; Nathanson, Katherine L.; Rebbeck, Timothy R.; Barkardottir, Rosa B.; Jakubowska, Anna; Lubinski, Jan; Durda, Katarzyna; Jaworska-Bieniek, Katarzyna; Claes, Kathleen; Van Maerken, Tom; Díez, Orland; Hansen, Thomas V.; Jønson, Lars; Gerdes, Anne Marie; Ejlertsen, Bent; De La Hoya, Miguel; Caldés, Trinidad; Dunning, Alison M.; Oliver, Clare; Fineberg, Elena; Cook, Margaret; Peock, Susan; McCann, Emma; Murray, Alex; Jacobs, Chris; Pichert, Gabriella; Lalloo, Fiona; Chu, Carol; Dorkins, Huw; Paterson, Joan; Ong, Kai Ren; Teixeira, Manuel R.; Teixeira, T.; Hogervorst, Frans B L; Van Der Hout, Annemarie H.; Seynaeve, Caroline; Van Der Luijt, Rob B.; Ligtenberg, Marjolijn J L; Devilee, Peter; Wijnen, Juul T.; Rookus, Matti A.; Meijers-Heijboer, Hanne E J; Blok, Marinus J.; Van Den Ouweland, Ans M W; Aalfs, Cora M.; Rodriguez, Gustavo C.; Phillips, Kelly Anne A; Piedmonte, Marion; Nerenstone, Stacy R.; Bae-Jump, Victoria L.; O'Malley, David M.; Ratner, Elena S.; Schmutzler, Rita K.; Wappenschmidt, Barbara; Rhiem, Kerstin; Engel, Christoph; Meindl, Alfons; Ditsch, Nina; Arnold, Norbert; Plendl, Hansjoerg J.; Niederacher, Dieter; Sutter, Christian; Wang-Gohrke, Shan; Steinemann, Doris; Preisler-Adams, Sabine; Kast, Karin; Varon-Mateeva, Raymonda; Gehrig, Andrea; Bojesen, Anders; Pedersen, Inge Sokilde; Sunde, Lone; Jensen, Uffe Birk; Thomassen, Mads; Kruse, Torben A.; Foretova, Lenka; Peterlongo, Paolo; Bernard, Loris; Peissel, Bernard; Scuvera, Giulietta; Manoukian, Siranoush; Radice, Paolo; Ottini, Laura; Montagna, Marco; Agata, Simona; Maugard, Christine; Simard, Jacques; Soucy, Penny; Berger, Andreas; Fink-Retter, Anneliese; Singer, Christian F.; Rappaport, Christine; Geschwantler-Kaulich, Daphne; Tea, Muy Kheng; Pfeiler, Georg; John, Esther M.; Miron, Alex; Neuhausen, Susan L.; Terry, Mary Beth; Chung, Wendy K.; Daly, Mary B.; Goldgar, David E.; Janavicius, Ramunas; Dorfling, Cecilia M.; Van Rensburg, Elisabeth J.; Fostira, Florentia; Konstantopoulou, Irene; Garber, Judy; Godwin, Andrew K.; Olah, Edith; Narod, Steven A.; Rennert, Gad; Paluch, Shani Shimon; Laitman, Yael; Friedman, Eitan; Liljegren, Annelie; Rantala, Johanna; Stenmark-Askmalm, Marie; Loman, Niklas; Imyanitov, Evgeny N.; Hamann, Ute; Spurdle, Amanda B.; Healey, Sue; Weitzel, Jeffrey N.; Herzog, Josef; Margileth, David; Gorrini, Chiara; Esteller, Manel; Gómez, Antonio; Sayols, Sergi; Vidal, Enrique; Heyn, Holger; Stoppa-Lyonnet, Dominique; Léoné, Melanie; Barjhoux, Laure; Fassy-Colcombet, Marion; De Pauw, Antoine; Lasset, Christine; Ferrer, Sandra Fert; Castera, Laurent; Berthet, Pascaline; Cornelis, François; Bignon, Yves Jean; Damiola, Francesca; Mazoyer, Sylvie; Sinilnikova, Olga M.; Maxwell, Christopher A.; Vijai, Joseph; Robson, Mark; Kauff, Noah; Corines, Marina J.; Villano, Danylko; Cunningham, Julie; Lee, Adam; Lindor, Noralane; Lázaro, Conxi; Easton, Douglas F.; Offit, Kenneth; Chenevix-Trench, Georgia; Couch, Fergus J.; Antoniou, Antonis C.; Pujana, Miguel Angel.
In: PLoS One, Vol. 10, No. 4, 120020, 01.04.2015.Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - Assessing associations between the AURKAHMMR-TPX2-TUBG1 functional module and breast cancer risk in BRCA1/2 mutation carriers
AU - Blanco, Ignacio
AU - Kuchenbaecker, Karoline
AU - Cuadras, Daniel
AU - Wang, Xianshu
AU - Barrowdale, Daniel
AU - De Garibay, Gorka Ruiz
AU - Librado, Pablo
AU - Sánchez-Gracia, Alejandro
AU - Rozas, Julio
AU - Bonifaci, Núria
AU - McGuffog, Lesley
AU - Pankratz, Vernon S.
AU - Islam, Abul
AU - Mateo, Francesca
AU - Berenguer, Antoni
AU - Petit, Anna
AU - Català, Isabel
AU - Brunet, Joan
AU - Feliubadaló, Lidia
AU - Tornero, Eva
AU - Benítez, Javier
AU - Osorio, Ana
AU - Teresa, Ramón
AU - Teresa, Cajal
AU - Nevanlinna, Heli
AU - Aittomäki, Kristiina
AU - Arun, Banu K.
AU - Toland, Amanda E.
AU - Karlan, Beth Y.
AU - Walsh, Christine
AU - Lester, Jenny
AU - Greene, Mark H.
AU - Mai, Phuong L.
AU - Nussbaum, Robert L.
AU - Andrulis, Irene L.
AU - Domchek, Susan M.
AU - Nathanson, Katherine L.
AU - Rebbeck, Timothy R.
AU - Barkardottir, Rosa B.
AU - Jakubowska, Anna
AU - Lubinski, Jan
AU - Durda, Katarzyna
AU - Jaworska-Bieniek, Katarzyna
AU - Claes, Kathleen
AU - Van Maerken, Tom
AU - Díez, Orland
AU - Hansen, Thomas V.
AU - Jønson, Lars
AU - Gerdes, Anne Marie
AU - Ejlertsen, Bent
AU - De La Hoya, Miguel
AU - Caldés, Trinidad
AU - Dunning, Alison M.
AU - Oliver, Clare
AU - Fineberg, Elena
AU - Cook, Margaret
AU - Peock, Susan
AU - McCann, Emma
AU - Murray, Alex
AU - Jacobs, Chris
AU - Pichert, Gabriella
AU - Lalloo, Fiona
AU - Chu, Carol
AU - Dorkins, Huw
AU - Paterson, Joan
AU - Ong, Kai Ren
AU - Teixeira, Manuel R.
AU - Teixeira, T.
AU - Hogervorst, Frans B L
AU - Van Der Hout, Annemarie H.
AU - Seynaeve, Caroline
AU - Van Der Luijt, Rob B.
AU - Ligtenberg, Marjolijn J L
AU - Devilee, Peter
AU - Wijnen, Juul T.
AU - Rookus, Matti A.
AU - Meijers-Heijboer, Hanne E J
AU - Blok, Marinus J.
AU - Van Den Ouweland, Ans M W
AU - Aalfs, Cora M.
AU - Rodriguez, Gustavo C.
AU - Phillips, Kelly Anne A
AU - Piedmonte, Marion
AU - Nerenstone, Stacy R.
AU - Bae-Jump, Victoria L.
AU - O'Malley, David M.
AU - Ratner, Elena S.
AU - Schmutzler, Rita K.
AU - Wappenschmidt, Barbara
AU - Rhiem, Kerstin
AU - Engel, Christoph
AU - Meindl, Alfons
AU - Ditsch, Nina
AU - Arnold, Norbert
AU - Plendl, Hansjoerg J.
AU - Niederacher, Dieter
AU - Sutter, Christian
AU - Wang-Gohrke, Shan
AU - Steinemann, Doris
AU - Preisler-Adams, Sabine
AU - Kast, Karin
AU - Varon-Mateeva, Raymonda
AU - Gehrig, Andrea
AU - Bojesen, Anders
AU - Pedersen, Inge Sokilde
AU - Sunde, Lone
AU - Jensen, Uffe Birk
AU - Thomassen, Mads
AU - Kruse, Torben A.
AU - Foretova, Lenka
AU - Peterlongo, Paolo
AU - Bernard, Loris
AU - Peissel, Bernard
AU - Scuvera, Giulietta
AU - Manoukian, Siranoush
AU - Radice, Paolo
AU - Ottini, Laura
AU - Montagna, Marco
AU - Agata, Simona
AU - Maugard, Christine
AU - Simard, Jacques
AU - Soucy, Penny
AU - Berger, Andreas
AU - Fink-Retter, Anneliese
AU - Singer, Christian F.
AU - Rappaport, Christine
AU - Geschwantler-Kaulich, Daphne
AU - Tea, Muy Kheng
AU - Pfeiler, Georg
AU - John, Esther M.
AU - Miron, Alex
AU - Neuhausen, Susan L.
AU - Terry, Mary Beth
AU - Chung, Wendy K.
AU - Daly, Mary B.
AU - Goldgar, David E.
AU - Janavicius, Ramunas
AU - Dorfling, Cecilia M.
AU - Van Rensburg, Elisabeth J.
AU - Fostira, Florentia
AU - Konstantopoulou, Irene
AU - Garber, Judy
AU - Godwin, Andrew K.
AU - Olah, Edith
AU - Narod, Steven A.
AU - Rennert, Gad
AU - Paluch, Shani Shimon
AU - Laitman, Yael
AU - Friedman, Eitan
AU - Liljegren, Annelie
AU - Rantala, Johanna
AU - Stenmark-Askmalm, Marie
AU - Loman, Niklas
AU - Imyanitov, Evgeny N.
AU - Hamann, Ute
AU - Spurdle, Amanda B.
AU - Healey, Sue
AU - Weitzel, Jeffrey N.
AU - Herzog, Josef
AU - Margileth, David
AU - Gorrini, Chiara
AU - Esteller, Manel
AU - Gómez, Antonio
AU - Sayols, Sergi
AU - Vidal, Enrique
AU - Heyn, Holger
AU - Stoppa-Lyonnet, Dominique
AU - Léoné, Melanie
AU - Barjhoux, Laure
AU - Fassy-Colcombet, Marion
AU - De Pauw, Antoine
AU - Lasset, Christine
AU - Ferrer, Sandra Fert
AU - Castera, Laurent
AU - Berthet, Pascaline
AU - Cornelis, François
AU - Bignon, Yves Jean
AU - Damiola, Francesca
AU - Mazoyer, Sylvie
AU - Sinilnikova, Olga M.
AU - Maxwell, Christopher A.
AU - Vijai, Joseph
AU - Robson, Mark
AU - Kauff, Noah
AU - Corines, Marina J.
AU - Villano, Danylko
AU - Cunningham, Julie
AU - Lee, Adam
AU - Lindor, Noralane
AU - Lázaro, Conxi
AU - Easton, Douglas F.
AU - Offit, Kenneth
AU - Chenevix-Trench, Georgia
AU - Couch, Fergus J.
AU - Antoniou, Antonis C.
AU - Pujana, Miguel Angel
PY - 2015/4/1
Y1 - 2015/4/1
N2 - While interplay between BRCA1 and AURKA-RHAMM-TPX2-TUBG1 regulates mammary epithelial polarization, common genetic variation in HMMR (gene product RHAMM) may be associated with risk of breast cancer in BRCA1 mutation carriers. Following on these observations, we further assessed the link between the AURKA-HMMR-TPX2-TUBG1 functional module and risk of breast cancer in BRCA1 or BRCA2 mutation carriers. Forty-one single nucleotide polymorphisms (SNPs) were genotyped in 15,252 BRCA1 and 8,211 BRCA2 mutation carriers and subsequently analyzed using a retrospective likelihood approach. The association of HMMR rs299290 with breast cancer risk in BRCA1 mutation carriers was confirmed: per-allele hazard ratio (HR) = 1.10, 95% confidence interval (CI) 1.04 - 1.15, p = 1.9 × 10-4 (false discovery rate (FDR)-adjusted p = 0.043). Variation in CSTF1, located next to AURKA, was also found to be associated with breast cancer risk in BRCA2 mutation carriers: rs2426618 per-allele HR = 1.10, 95% CI 1.03 - 1.16, p = 0.005 (FDR-adjusted p = 0.045). Assessment of pairwise interactions provided suggestions (FDR-adjusted pinteraction values > 0.05) for deviations from the multiplicative model for rs299290 and CSTF1 rs6064391, and rs299290 and TUBG1 rs11649877 in both BRCA1 and BRCA2 mutation carriers. Following these suggestions, the expression of HMMR and AURKA or TUBG1 in sporadic breast tumors was found to potentially interact, influencing patients' survival. Together, the results of this study support the hypothesis of a causative link between altered function of AURKA-HMMR-TPX2-TUBG1 and breast carcinogenesis in BRCA1/2 mutation carriers.
AB - While interplay between BRCA1 and AURKA-RHAMM-TPX2-TUBG1 regulates mammary epithelial polarization, common genetic variation in HMMR (gene product RHAMM) may be associated with risk of breast cancer in BRCA1 mutation carriers. Following on these observations, we further assessed the link between the AURKA-HMMR-TPX2-TUBG1 functional module and risk of breast cancer in BRCA1 or BRCA2 mutation carriers. Forty-one single nucleotide polymorphisms (SNPs) were genotyped in 15,252 BRCA1 and 8,211 BRCA2 mutation carriers and subsequently analyzed using a retrospective likelihood approach. The association of HMMR rs299290 with breast cancer risk in BRCA1 mutation carriers was confirmed: per-allele hazard ratio (HR) = 1.10, 95% confidence interval (CI) 1.04 - 1.15, p = 1.9 × 10-4 (false discovery rate (FDR)-adjusted p = 0.043). Variation in CSTF1, located next to AURKA, was also found to be associated with breast cancer risk in BRCA2 mutation carriers: rs2426618 per-allele HR = 1.10, 95% CI 1.03 - 1.16, p = 0.005 (FDR-adjusted p = 0.045). Assessment of pairwise interactions provided suggestions (FDR-adjusted pinteraction values > 0.05) for deviations from the multiplicative model for rs299290 and CSTF1 rs6064391, and rs299290 and TUBG1 rs11649877 in both BRCA1 and BRCA2 mutation carriers. Following these suggestions, the expression of HMMR and AURKA or TUBG1 in sporadic breast tumors was found to potentially interact, influencing patients' survival. Together, the results of this study support the hypothesis of a causative link between altered function of AURKA-HMMR-TPX2-TUBG1 and breast carcinogenesis in BRCA1/2 mutation carriers.
UR - http://www.scopus.com/inward/record.url?scp=84927153607&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84927153607&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0120020
DO - 10.1371/journal.pone.0120020
M3 - Article
AN - SCOPUS:84927153607
VL - 10
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 4
M1 - 120020
ER -