Dataset Information

AURKA F31I polymorphism and breast cancer risk in BRCA1 and BRCA2 mutation carriers: a consortium of investigators of modifiers of BRCA1/2 study.

ABSTRACT: The AURKA oncogene is associated with abnormal chromosome segregation and aneuploidy and predisposition to cancer. Amplification of AURKA has been detected at higher frequency in tumors from BRCA1 and BRCA2 mutation carriers than in sporadic breast tumors, suggesting that overexpression of AURKA and inactivation of BRCA1 and BRCA2 cooperate during tumor development and progression. The F31I polymorphism in AURKA has been associated with breast cancer risk in the homozygous state in prior studies. We evaluated whether the AURKA F31I polymorphism modifies breast cancer risk in BRCA1 and BRCA2 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2. Consortium of Investigators of Modifiers of BRCA1/2 was established to provide sufficient statistical power through increased numbers of mutation carriers to identify polymorphisms that act as modifiers of cancer risk and can refine breast cancer risk estimates in BRCA1 and BRCA2 mutation carriers. A total of 4,935 BRCA1 and 2,241 BRCA2 mutation carriers and 11 individuals carrying both BRCA1 and BRCA2 mutations was genotyped for F31I. Overall, homozygosity for the 31I allele was not significantly associated with breast cancer risk in BRCA1 and BRCA2 carriers combined [hazard ratio (HR), 0.91; 95% confidence interval (95% CI), 0.77-1.06]. Similarly, no significant association was seen in BRCA1 (HR, 0.90; 95% CI, 0.75-1.08) or BRCA2 carriers (HR, 0.93; 95% CI, 0.67-1.29) or when assessing the modifying effects of either bilateral prophylactic oophorectomy or menopausal status of BRCA1 and BRCA2 carriers. In summary, the F31I polymorphism in AURKA is not associated with a modified risk of breast cancer in BRCA1 and BRCA2 carriers.

SUBMITTER: Couch FJ

PROVIDER: S-EPMC2775799 | biostudies-literature | 2007 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

AURKA F31I polymorphism and breast cancer risk in BRCA1 and BRCA2 mutation carriers: a consortium of investigators of modifiers of BRCA1/2 study.

Couch Fergus J FJ Sinilnikova Olga O Vierkant Robert A RA Pankratz V Shane VS Fredericksen Zachary S ZS Stoppa-Lyonnet Dominique D Coupier Isabelle I Hughes David D Hardouin Agnès A Berthet Pascaline P Peock Susan S Cook Margaret M Baynes Caroline C Hodgson Shirley S Morrison Patrick J PJ Porteous Mary E ME Jakubowska Anna A Lubinski Jan J Gronwald Jacek J Spurdle Amanda B AB Schmutzler Rita R Versmold Beatrix B Engel Christoph C Meindl Alfons A Sutter Christian C Horst Jurgen J Schaefer Dieter D Offit Kenneth K Kirchhoff Tomas T Andrulis Irene L IL Ilyushik Eduard E Glendon Gordon G Devilee Peter P Vreeswijk Maaike P G MP Vasen Hans F A HF Borg Ake A Backenhorn Katja K Struewing Jeffery P JP Greene Mark H MH Neuhausen Susan L SL Rebbeck Timothy R TR Nathanson Katherine K Domchek Susan S Wagner Theresa T Garber Judy E JE Szabo Csilla C Zikan Michal M Foretova Lenka L Olson Janet E JE Sellers Thomas A TA Lindor Noralane N Nevanlinna Heli H Tommiska Johanna J Aittomaki Kristiina K Hamann Ute U Rashid Muhammad U MU Torres Diana D Simard Jacques J Durocher Francine F Guenard Frederic F Lynch Henry T HT Isaacs Claudine C Weitzel Jeffrey J Olopade Olufunmilayo I OI Narod Steven S Daly Mary B MB Godwin Andrew K AK Tomlinson Gail G Easton Douglas F DF Chenevix-Trench Georgia G Antoniou Antonis C AC

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20070701 7

The AURKA oncogene is associated with abnormal chromosome segregation and aneuploidy and predisposition to cancer. Amplification of AURKA has been detected at higher frequency in tumors from BRCA1 and BRCA2 mutation carriers than in sporadic breast tumors, suggesting that overexpression of AURKA and inactivation of BRCA1 and BRCA2 cooperate during tumor development and progression. The F31I polymorphism in AURKA has been associated with breast cancer risk in the homozygous state in prior studies ...[more]

PMID: 17627006

Similar Datasets

Project description:INTRODUCTION:Previous studies have demonstrated that common breast cancer susceptibility alleles are differentially associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers. It is currently unknown how these alleles are associated with different breast cancer subtypes in BRCA1 and BRCA2 mutation carriers defined by estrogen (ER) or progesterone receptor (PR) status of the tumour. METHODS:We used genotype data on up to 11,421 BRCA1 and 7,080 BRCA2 carriers, of whom 4,310 had been affected with breast cancer and had information on either ER or PR status of the tumour, to assess the associations of 12 loci with breast cancer tumour characteristics. Associations were evaluated using a retrospective cohort approach. RESULTS:The results suggested stronger associations with ER-positive breast cancer than ER-negative for 11 loci in both BRCA1 and BRCA2 carriers. Among BRCA1 carriers, single nucleotide polymorphism (SNP) rs2981582 (FGFR2) exhibited the biggest difference based on ER status (per-allele hazard ratio (HR) for ER-positive = 1.35, 95% CI: 1.17 to 1.56 vs HR = 0.91, 95% CI: 0.85 to 0.98 for ER-negative, P-heterogeneity = 6.5 × 10-6). In contrast, SNP rs2046210 at 6q25.1 near ESR1 was primarily associated with ER-negative breast cancer risk for both BRCA1 and BRCA2 carriers. In BRCA2 carriers, SNPs in FGFR2, TOX3, LSP1, SLC4A7/NEK10, 5p12, 2q35, and 1p11.2 were significantly associated with ER-positive but not ER-negative disease. Similar results were observed when differentiating breast cancer cases by PR status. CONCLUSIONS:The associations of the 12 SNPs with risk for BRCA1 and BRCA2 carriers differ by ER-positive or ER-negative breast cancer status. The apparent differences in SNP associations between BRCA1 and BRCA2 carriers, and non-carriers, may be explicable by differences in the prevalence of tumour subtypes. As more risk modifying variants are identified, incorporating these associations into breast cancer subtype-specific risk models may improve clinical management for mutation carriers.

Dataset Information

AURKA F31I polymorphism and breast cancer risk in BRCA1 and BRCA2 mutation carriers: a consortium of investigators of modifiers of BRCA1/2 study.

Publications

AURKA F31I polymorphism and breast cancer risk in BRCA1 and BRCA2 mutation carriers: a consortium of investigators of modifiers of BRCA1/2 study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets