Assessing associations between the AURKAHMMR-TPX2-TUBG1 functional module and breast cancer risk in BRCA1/2 mutation carriers Journal Article
| Authors: | Blanco, I.; Kuchenbaecker, K.; Cuadras, D.; Wang, X.; Barrowdale, D.; De Garibay, G. R.; Librado, P.; Sanchez-Garcia, A.; Rozas, J.; Bonifaci, N.; McGuffog, L.; Pankratz, V. S.; Isliam, A.; Mateo, F.; Berenguer, A.; Petit, A.; Catala, I.; Brunet, J.; Feliubadalo, L.; Tornero, E.; Benitez, J.; Osorio, A.; Ramon y Cajal, T.; Nevanlinna, H.; Aittomaki, K.; Arun, B. K.; Toland, A. E.; Karlan, B. Y.; Walsh, C.; Lester, J.; Greene, M. H.; Mai, P, L.; Nussbaum, R. L.; Andrulis, I. L.; Domchek, S. M.; Nathanson, K. L.; Durda, K.; Jaworska-Bieniek, K.; Claes, K.; Van Maerken, T.; Diez, O.; Hansen, T. V.; Jonson, L.; Gerdes, A. M.; Ejlertsen, B.; de la Hoya, M.; Caldes, T.; Dunning, A. M.; Oliver, C.; Fineberg, E.; Cook, M.; Peock, S.; McCann, E.; Murray, A.; Jacobs, C.; Pichert, G.; Lalloo, F.; Chu, C.; Dorkins, H.; Paterson, J.; Ong, K. R.; Teixeira, M. R.; Hogervorst, F. B. L.; van der Hout, A. H.; Seynaeve, C.; van der Luijt, R. B.; Ligtenberg, M. J. L.; Devilee, P.; Wijnen, J. T.; Rookus, M. A.; Meijers-Heijboer, H. E. J.; Blok, M. J.; van den Ouweland, A. M. W.; Aalfs, C. M.; Rodriguez, G. C.; Phillips, K. A. A.; Piedmonte, M.; Nerenstone, S. R.; Bae-Jump, V. L.; O'Malley, D. M.; Ratner, E. S.; Schmutzler, R. K.; Wappenschmidt, B.; Rhiem, K.; Engel, C.; Meindl, A.; Ditsch, N.; Arnold, N.; Plendl, H. J.; Niederacher, D.; Sutter, C.; Wang-Gohrke, S.; Steinemann, D.; Preisler-Adams, S.; Kast, K.; Varon-Mateeva, R.; Gehrig, A.; Bojesen, A.; Pedersen, I. S.; Sunde, L.; Jensen, U. B.; Thomassen, M.; Kruse, T. A.; Foretova, L.; Peterlongo, P.; Bernard, L.; Peissel, B.; Scuvera, G.; Manoukian, S.; Radice, P.; Ottini, L.; Montagna, M.; Agata, S.; Maugard, C.; Simard, J.; Soucy, P.; Berger, A.; Fink-Retter, A.; Singer, C. F.; Rappaport, C.; Geschwantler-Kaulich, D.; Tea, M. K.; Pfeiler, G.; BCFR; John, E. M.; Miron, A.; Neuhausen, S. L.; Terry, M. B.; Chung, W. K.; Daly, M. B.; Goldgar, D. E.; Janavicius, R.; Dorfling, C. M.; van Rensburg, E. J.; Fostira, F.; Konstantopoulou, I.; Garber, J.; Godwin, A. K.; Olah, E.; Narod, S. A.; Rennert, G.; Shimon Paluch, S.; Laitman, Y.; Friedman, E.; SWE-BRCA; Liljegren, A.; Rantala, J.; Stenkmark-Askmalm, M.; Loman, N.; Imyanitov, E. N.; Hamann, U.; kConFab Investigators; Spurdle, A. B.; Healey, S.; Weitzel, J. N.; Herzog, J.; Margileth, D.; Gorrini, C.; Esteller, M.; Gomez, A.; Sayols, S.; Vidal, E.; Heyn, H.; GEMO; Stoppa-Lyonnet, D.; Leone, M.; Barjhoux, L.; Fassy-Colcombet, M.; de Pauw, A.; Lasset, C.; Fert Ferrer, S.; Castera, L.; Berthet, P.; Cornelis, F.; Bignon, Y. J.; Damiola, F.; Mazoyer, S.; Sinilnikova, O. M.; Maxwell, C. A.; Vijai, J.; Robson, M.; Kauff, N.; Corines, M. J.; Villano, D.; Cunningham, J.; Lee, A.; Noralane, L.; Lazaro, C.; Easton, D. F.; Offit, K.; Chenevix-Trench, G.; Couch, F. J.; Antoniou, A. C.; Pujana, M. A. |
| Article Title: | Assessing associations between the AURKAHMMR-TPX2-TUBG1 functional module and breast cancer risk in BRCA1/2 mutation carriers |
| 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<inf>-4</inf> (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 p<inf>interaction</inf> 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. |
| Keywords: | cancer survival; controlled study; gene mutation; human cell; major clinical study; single nucleotide polymorphism; cancer risk; gene; breast cancer; gene expression; genetic association; genetic variability; genotype; retrospective study; tumor suppressor gene; gene interaction; genetic risk; breast carcinogenesis; aurka gene; human; article; cstf1 gene; hmmr gene; tpx2 gene; tubg1 gene |
| Journal Title: | PLoS ONE |
| Volume: | 10 |
| Issue: | 4 |
| ISSN: | 1932-6203 |
| Publisher: | Public Library of Science |
| Date Published: | 2015-04-01 |
| Start Page: | e0120020 |
| Language: | English |
| DOI: | 10.1371/journal.pone.0120020 |
| PROVIDER: | scopus |
| PMCID: | PMC4382299 |
| PUBMED: | 25830658 |
| DOI/URL: | |
| Notes: | Export Date: 4 May 2015 -- Source: Scopus |
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