Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/96590
Title: Assessing Associations between the AURKA-HMMR-TPX2-TUBG1 Functional Module and Breast Cancer Risk in BRCA1/2 Mutation Carriers
Author: Blanco Guillermo, Ignacio
Cuadras, Daniel
Ruiz de Garibay, Gorka
Librado Sanz, Pablo
Sánchez-Gracia, Alejandro
Rozas Liras, Julio A.
Bonifaci, Núria
Mateo González, Francesca
Berenguer, Antoni
Petit, Anna
Català, Isabel
Feliubadaló i Elorza, Maria Lídia
Tornero, Eva
Lázaro García, Conxi
Pujana Genestar, M. Ángel
Esteller, Manel
Gómez, Antonio
Sayols, Sergi
Vidal, Enrique
Heyn, Holger
Keywords: Càncer de mama
Mutació (Biologia)
Càncer d'ovari
Seqüència d'aminoàcids
Breast cancer
Mutation (Biology)
Ovarian cancer
Amino acid sequence
Issue Date: 1-Apr-2015
Publisher: Public Library of Science (PLoS)
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 x 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.
Note: Reproducció del document publicat a: http://dx.doi.org/10.1371/journal.pone.0120020
It is part of: PLoS One, 2015, vol. 10, num. 4, p. e01200204
Related resource: http://dx.doi.org/10.1371/journal.pone.0120020
URI: http://hdl.handle.net/2445/96590
ISSN: 1932-6203
Appears in Collections:Articles publicats en revistes (Genètica, Microbiologia i Estadística)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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