Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

Assessing associations between the AURKA-HMMR-TPX2-TUBG1 functional module and breast cancer risk in BRCA1/2 mutation carriers

Research output: Contribution to journalJournal articleResearchpeer-review

  1. Dancing with atrial fibrillation - How arrhythmia affects everyday life of family members: A qualitative study

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Insulin resistance genetic risk score and burden of coronary artery disease in patients referred for coronary angiography

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Precursors of self-reported subclinical hypomania in adolescence: A longitudinal general population study

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Genetic markers of abdominal obesity and weight loss after gastric bypass surgery

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Cohort profile and heritability assessment of familial pancreatic cancer: a nation-wide study

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Oral contraceptive use and ovarian cancer risk for BRCA1/2 mutation carriers: an international cohort study

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Variation in the risk of colorectal cancer in families with Lynch syndrome: a retrospective cohort study

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Direct to consumer genetic testing in Denmark-public knowledge, use, and attitudes

    Research output: Contribution to journalJournal articleResearchpeer-review

  • Ignacio Blanco
  • Karoline Kuchenbaecker
  • Daniel Cuadras
  • Xianshu Wang
  • Daniel Barrowdale
  • Gorka Ruiz de Garibay
  • Pablo Librado
  • Alejandro Sánchez-Gracia
  • Julio Rozas
  • Núria Bonifaci
  • Lesley McGuffog
  • Vernon S Pankratz
  • Abul Islam
  • Francesca Mateo
  • Antoni Berenguer
  • Anna Petit
  • Isabel Català
  • Joan Brunet
  • Lidia Feliubadaló
  • Eva Tornero
  • Javier Benítez
  • Ana Osorio
  • Teresa Ramón y Cajal
  • Heli Nevanlinna
  • Kristiina Aittomäki
  • Banu K Arun
  • Amanda E Toland
  • Beth Y Karlan
  • Christine Walsh
  • Jenny Lester
  • Mark H Greene
  • Phuong L Mai
  • Robert L Nussbaum
  • Irene L Andrulis
  • Susan M Domchek
  • Katherine L Nathanson
  • Timothy R Rebbeck
  • Rosa B Barkardottir
  • Anna Jakubowska
  • Jan Lubinski
  • Katarzyna Durda
  • Katarzyna Jaworska-Bieniek
  • Kathleen Claes
  • Tom Van Maerken
  • Orland Díez
  • Thomas V Hansen
  • Lars Jønson
  • Anne-Marie Gerdes
  • Bent Ejlertsen
  • Miguel de la Hoya
  • Teixeira
View graph of relations

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.

Original languageEnglish
JournalP L o S One
Volume10
Issue number4
Pages (from-to)e0120020
ISSN1932-6203
DOIs
Publication statusPublished - 2015

ID: 45844234