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.

Abramson Cancer Center and Center for Clinical Epidemiology and Biostatistics The University of Pennsylvania Perelman School of Medicine Philadelphia Pennsylvania United States of America

Abramson Cancer Center and Department of Medicine The University of Pennsylvania School of Medicine Philadelphia Pennsylvania United States of America

All Wales Medical Genetics Service Glan Clwyd Hospital Rhyl United Kingdom

All Wales Medical Genetics Services Singleton Hospital Swansea United Kingdom

Breast Cancer and Systems Biology Unit Catalan Institute of Oncology L'Hospitalet del Llobregat Catalonia Spain

Cancer Epigenetics and Biology Program Barcelona Catalonia Spain

Cancer Epigenetics and Biology Program IDIBELL L'Hospitalet del Llobregat Catalonia Spain

Cancer Genetics Laboratory Department of Genetics University of Pretoria Arcadia South Africa

Cancer Genomics Laboratory Centre Hospitalier Universitaire de Québec Research Center and Laval University Quebec City Canada

Center for Cancer Genetics and Prevention Dana Farber Cancer Institute Harvard Medical School Boston Massachusetts United States of America

Center for Genomic Medicine Rigshospitalet Copenhagen University Hospital Copenhagen Denmark

Center for Individualized Medicine Mayo Clinic Scottsdale Arizona United States of America

Center for Medical Genetics Ghent University Ghent Belgium

Central Connecticut Cancer Consortium Hartford Hospital Helen and Harry Gray Cancer Center Hartford Connecticut United States of America

Centre François Baclesse Caen France

Centre of Familial Breast and Ovarian Cancer and Centre for Integrated Oncology University Hospital of Cologne Cologne Germany

Centre of Familial Breast and Ovarian Cancer Department of Medical Genetics Institute of Human Genetics University Würzburg Würzburg Germany

Clalit National Israeli Cancer Control Center and Department of Community Medicine and Epidemiology Carmel Medical Center and B Rappaport Faculty of Medicine Haifa Israel

Clinical Cancer Genetics City of Hope Duarte California United States of America

Clinical Genetics Branch Division of Cancer Epidemiology and Genetics National Cancer Institute Maryland Rockville United States of America

Clinical Genetics Guy's and St Thomas' National Health Service Foundation Trust London United Kingdom

Clinical Genetics Research Laboratory Memorial Sloan Kettering Cancer Center New York New York United States of America

Département d'Oncogénétique Centre Jean Perrin Université de Clermont Ferrand Clermont Ferrand France

Department of Cancer Biology Dana Farber Cancer Institute Boston Massachusetts United States of America

Department of Cancer Epidemiology and Genetics Masaryk Memorial Cancer Institute Brno Czech Republic

Department of Clinical Genetics Aarhus University Hospital Aarhus Denmark

Department of Clinical Genetics Academic Medical Center Amsterdam The Netherlands

Department of Clinical Genetics East Anglian Regional Genetics Service Addenbrookes Hospital Cambridge United Kingdom

Department of Clinical Genetics Erasmus University Medical Center Rotterdam The Netherlands

Department of Clinical Genetics Fox Chase Cancer Center Philadelphia Pennsylvania United States of America

Department of Clinical Genetics Helsinki University Central Hospital Helsinki Finland

Department of Clinical Genetics Karolinska University Hospital Stockholm Sweden

Department of Clinical Genetics Maastricht University Medical Center Maastricht The Netherlands

Department of Clinical Genetics Odense University Hospital Odense Denmark

Department of Clinical Genetics Rigshospitalet Copenhagen University Hospital Copenhagen Denmark

Department of Clinical Genetics Vejle Hospital Vejle Denmark

Department of Clinical Genetics Vrije Universiteit University Medical Centre Amsterdam The Netherlands

Department of Dermatology University of Utah School of Medicine Salt Lake City Utah United States of America

Department of Epidemiology Cancer Prevention Institute of California Fremont California United States of America

Department of Epidemiology Columbia University New York New York United States of America

Department of Epidemiology Netherlands Cancer Institute Amsterdam The Netherlands

Department of Experimental Oncology Istituto Europeo di Oncologia Cogentech Cancer Genetic Test Laboratory Milan Italy

Department of Genetic Engineering and Biotechnology University of Dhaka Dhaka Bangladesh

Department of Genetics and Biodiversity Research Institute University of Barcelona Barcelona Catalonia Spain

Department of Genetics and Pathology Pomeranian Medical University Szczecin Poland

Department of Genetics Portuguese Oncology Institute and Biomedical Sciences Institute Porto University Porto Portugal

Department of Genetics University Medical Centre Groningen University of Groningen Groningen Netherlands

Department of Gynecology and Obstetrics and Comprehensive Cancer Center Medical University of Vienna Vienna Austria

Department of Gynecology and Obstetrics Christian Albrechts University of Kiel University Medical Center Schleswig Holstein Kiel Germany

Department of Gynecology and Obstetrics Division of Tumor Genetics Klinikum Rechts der Isar Technical University Munich Munich Germany

Department of Gynecology and Obstetrics Ludwig Maximilian University Munich Munich Germany

Department of Gynecology and Obstetrics University Hospital Carl Gustav Carus Technical University Dresden Dresden Germany

Department of Gynecology and Obstetrics University Hospital Düsseldorf Heinrich Heine University Düsseldorf Düsseldorf Germany

Department of Gynecology and Obstetrics University Hospital Ulm Ulm Germany

Department of Health Sciences Research Mayo Clinic Rochester Minnesota United States of America

Department of Human Genetics and Department of Pathology Radboud university medical center Nijmegen The Netherlands

Department of Human Genetics Leiden University Medical Center Leiden The Netherlands; Department of Clinical Genetics Leiden University Medical Center Leiden The Netherlands

Department of Human Genetics Leiden University Medical Center Leiden The Netherlands; Department of Pathology Leiden University Medical Center Leiden The Netherlands

Department of Laboratory Medicine and Pathology Mayo Clinic Rochester United States of America

Department of Laboratory Medicine and Pathology Mayo Clinic Rochester United States of America; Department of Health Sciences Research Mayo Clinic Rochester Minnesota United States of America

Department of Medical Genetics University Medical Center Utrecht Utrecht The Netherlands

Department of Medical Oncology Family Cancer Clinic Erasmus University Medical Center Rotterdam The Netherlands

Department of Medicine and Genetics University of California San Francisco San Francisco California United States of America

Department of Molecular Genetics National Institute of Oncology Budapest Hungary

Department of Molecular Medicine Sapienza University Rome Italy

Department of Obstetrics and Gynecology University of Helsinki and Helsinki University Central Hospital Helsinki Finland

Department of Oncology Karolinska University Hospital Stockholm Sweden

Department of Oncology Lund University Hospital Lund Sweden

Department of Oncology Mayo Clinic Rochester Minnesota United States of America

Department of Oncology Rigshospitalet Copenhagen University Hospital Copenhagen Denmark

Department of Pathology and Laboratory Medicine University of Kansas Medical Center Kansas City Kansas United States of America

Department of Pathology Landspitali University Hospital and BMC Faculty of Medicine University of Iceland Reykjavik Iceland

Department of Pathology University Hospital of Bellvitge Bellvitge Institute for Biomedical Research L'Hospitalet del Llobregat Catalonia Spain

Department of Pediatrics Child and Family Research Institute University of British Columbia Vancouver Canada

Department of Population Sciences Beckman Research Institute of City of Hope Duarte California United States of America

Department of Tumour Biology Institut Curie Paris France

Department of Tumour Biology Institut Curie Paris France; Institut National de la Santé et de la Recherche Médicale U830 Institut Curie Paris France; Université Paris Descartes Sorbonne Paris Cité Paris France

Departments of Pediatrics and Medicine Columbia University Medical Center New York New York United States of America

Division of Cancer Medicine Peter MacCallum Cancer Centre East Melbourne Victoria Australia

Division of Cancer Medicine University of Texas MD Anderson Cancer Center Houston Texas United States of America

Division of Clinical Genetics Department of Clinical and Experimental Medicine Linköping University Linköping Sweden

Division of Gynecologic Oncology Department of Obstetrics and Gynecology University of North Carolina Chapel Hill North Carolina United States of America

Division of Gynecologic Oncology NorthShore University HealthSystem University of Chicago Chicago Illinois United States of America

Division of Gynecologic Oncology Ohio State University Columbus Cancer Council Hilliard Ohio United States of America

Division of Gynecologic Oncology Yale University School of Medicine New Haven Connecticut United States of America

Division of Human Cancer Genetics Departments of Internal Medicine and Molecular Virology Immunology and Medical Genetics Comprehensive Cancer Center The Ohio State University Columbus Ohio United States of America

Epidemiological Study of Familial Breast Cancer Centre for Cancer Genetic Epidemiology Department of Public Health and Primary Care University of Cambridge Strangeways Research Laboratory Cambridge United Kingdom

Family Cancer Clinic Netherlands Cancer Institute Amsterdam The Netherlands

Fondazione Istituto di Oncologia Molecolare Milan Italy

Genetic Medicine Manchester Academic Health Sciences Centre Central Manchester University Hospitals National Health Service Foundation Trust Manchester United Kingdom

Genetic Unit Avicenne Hospital Assitance Publique Hôpitaux de Paris Paris Sud Francilien Hospital Evry Corbeil and University Hospital Clermont Ferrand France

Gynecologic Oncology Group Statistical and Data Center Roswell Park Cancer Institute Buffalo New York United States of America

Hereditary Cancer Program Catalan Institute of Oncology Hospital Josep Trueta Girona Catalonia Spain

Hereditary Cancer Program Catalan Institute of Oncology L'Hospitalet del Llobregat Catalonia Spain

Human Genetics Group Spanish National Cancer Centre and Biomedical Network on Rare Diseases Madrid Spain

Immunology and Molecular Oncology Unit Istituto Oncologico Veneto Padua Italy

Institut National de la Santé et de la Recherche Médicale UMR5286 Université Lyon 1 Centre de Recherche en Cancérologie de Lyon Lyon France

Institute for Medical Informatics Statistics and Epidemiology University of Leipzig Leipzig Germany

Institute of Cell and Molecular Pathology Hannover Medical School Hannover Germany

Institute of Human Genetics Campus Virchov Klinikum Charite Berlin Berlin Germany

Institute of Human Genetics Christian Albrechts University of Kiel University Medical Center Schleswig Holstein Kiel Germany

Institute of Human Genetics Department of Human Genetics University Hospital Heidelberg Heidelberg Germany

Institute of Human Genetics University of Münster Münster Germany

Laboratoire de Diagnostic Génétique et Service d'Onco Hématologie Hopitaux Universitaire de Strasbourg Centre Hospitalier Régional Universitaire Nouvel Hôpital Civil Strasbourg France

Laboratoire de Génétique Chromosomique Hôtel Dieu Centre Hospitalier Chambéry France

Molecular Diagnostics Laboratory Institute of Radioisotopes and Radiodiagnostic Products National Centre for Scientific Research Demokritos Athens Greece

Molecular Genetics of Breast Cancer German Cancer Research Center Heidelberg Germany

Molecular Oncology Laboratory Hospital Clínico San Carlos San Carlos Research Institute Madrid Spain

N N Petrov Institute of Oncology St Petersburg Russia

North West Thames Regional Genetics Service Kennedy Galton Centre Harrow United Kingdom

Oncogenetics Group Vall d'Hebron Institute of Oncology and Universitat Autònoma de Barcelona Barcelona Catalonia Spain

Oncology Service Hospital de la Santa Creu i Sant Pau Barcelona Catalonia Spain

Queensland Institute of Medical Research Berghofer Medical Research Institute Brisbane Australia

Samuel Lunenfeld Research Institute Mount Sinai Hospital and Departments of Molecular Genetics and Laboratory Medicine and Pathobiology University of Toronto Toronto Ontario Canada

Section of Molecular Diagnostics Department of Biochemistry Aalborg University Hospital Aalborg Denmark

St Joseph Hospital of Orange Care of City of Hope Clinical Cancer Genetics Community Research Network Duarte California United States of America

Statistics Unit Bellvitge Institute for Biomedical Research L'Hospitalet del Llobregat Catalonia Spain

The Campbell Family Institute for Breast Cancer Research Ontario Cancer Institute University Health Network Toronto Canada

The Institute of Oncology Chaim Sheba Medical Center Ramat Gan Israel

The Susanne Levy Gertner Oncogenetics Unit Institute of Human Genetics Chaim Sheba Medical Center Ramat Gan Israel

The Susanne Levy Gertner Oncogenetics Unit Institute of Human Genetics Chaim Sheba Medical Center Ramat Gan Israel; Sackler Faculty of Medicine Tel Aviv University Ramat Aviv Israel

Unit of Medical Genetics Department of Preventive and Predictive Medicine Istituto di Ricovero e Cura a Carattere Scientifico Milan Italy

Unit of Molecular Bases of Genetic Risk and Genetic Testing Department of Preventive and Predictive Medicine Istituto di Ricovero e Cura a Carattere Scientifico Milan Italy

Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents Hospices Civils de Lyon Centre Léon Bérard Lyon France

Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents Hospices Civils de Lyon Centre Léon Bérard Lyon France; Institut National de la Santé et de la Recherche Médicale UMR5286 Université Lyon 1 Centre de Recherche en Cancérologie de Lyon Lyon France

Université Lyon 1 Centre National de la Recherche Scientifique UMR5558 and Unité de Prévention et d'Epidémiologie Génétique Centre Léon Bérard Lyon France

Vilnius University Hospital Santariskiu Clinics Hematology Oncology and Transfusion Medicine Center Department of Molecular and Regenerative Medicine State Research Centre Institute for Innovative medicine Vilnius Lithuania

West Midlands Regional Genetics Service Birmingham Women's Hospital Healthcare National Health Service Trust Edgbaston Birmingham United Kingdom

Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute Cedars Sinai Medical Center Los Angeles California United States of America

Women's College Research Institute University of Toronto Toronto Canada

Yorkshire Regional Genetics Service Leeds United Kingdom

Zobrazit více v PubMed

Pujana MA, Han JD, Starita LM, Stevens KN, Tewari M, Ahn JS, et al. Network modeling links breast cancer susceptibility and centrosome dysfunction. Nat Genet. 2007;39: 1338–1349. PubMed

Kalmyrzaev B, Pharoah PD, Easton DF, Ponder BA, Dunning AM Hyaluronan-mediated motility receptor gene single nucleotide polymorphisms and risk of breast cancer. Cancer Epidemiol Biomarkers Prev. 2008;17: 3618–3620. 10.1158/1055-9965.EPI-08-0216 PubMed DOI

Hunter DJ, Kraft P, Jacobs KB, Cox DG, Yeager M, Hankinson SE, et al. A genome-wide association study identifies alleles in FGFR2 associated with risk of sporadic postmenopausal breast cancer. Nat Genet. 2007;39: 870–874. PubMed PMC

Maxwell CA, Benitez J, Gomez-Baldo L, Osorio A, Bonifaci N, Fernandez-Ramires R, et al. Interplay between BRCA1 and RHAMM regulates epithelial apicobasal polarization and may influence risk of breast cancer. PLoS Biol. 2011;9: e1001199 10.1371/journal.pbio.1001199 PubMed DOI PMC

Couch FJ, Sinilnikova O, Vierkant RA, Pankratz VS, Fredericksen ZS, Stoppa-Lyonnet D, et al. AURKA F31I polymorphism and breast cancer risk in BRCA1 and BRCA2 mutation carriers: a consortium of investigators of modifiers of BRCA1/2 study. Cancer Epidemiol Biomarkers Prev. 2007;16: 1416–1421. PubMed PMC

Olson JE, Wang X, Pankratz VS, Fredericksen ZS, Vachon CM, Vierkant RA, et al. Centrosome-related genes, genetic variation, and risk of breast cancer. Breast Cancer Res Treat. 2011;125: 221–228. 10.1007/s10549-010-0950-8 PubMed DOI PMC

Hartman JLt, Garvik B, Hartwell L Principles for the buffering of genetic variation. Science. 2001;291: 1001–1004. PubMed

Dixon SJ, Costanzo M, Baryshnikova A, Andrews B, Boone C Systematic mapping of genetic interaction networks. Annu Rev Genet. 2009;43: 601–625. 10.1146/annurev.genet.39.073003.114751 PubMed DOI

Costanzo M, Baryshnikova A, Bellay J, Kim Y, Spear ED, Sevier CS, et al. The genetic landscape of a cell. Science. 2010;327: 425–431. 10.1126/science.1180823 PubMed DOI PMC

Bonifaci N, Colas E, Serra-Musach J, Karbalai N, Brunet J, Gomez A, et al. Integrating gene expression and epidemiological data for the discovery of genetic interactions associated with cancer risk. Carcinogenesis. 2014;35: 578–585. 10.1093/carcin/bgt403 PubMed DOI

Couch FJ, Wang X, McGuffog L, Lee A, Olswold C, Kuchenbaecker KB, et al. Genome-wide association study in BRCA1 mutation carriers identifies novel loci associated with breast and ovarian cancer risk. PLoS Genet. 2013;9: e1003212 10.1371/journal.pgen.1003212 PubMed DOI PMC

Gaudet MM, Kuchenbaecker KB, Vijai J, Klein RJ, Kirchhoff T, McGuffog L, et al. Identification of a BRCA2-specific modifier locus at 6p24 related to breast cancer risk. PLoS Genet. 2013;9: e1003173 10.1371/journal.pgen.1003173 PubMed DOI PMC

Michailidou K, Hall P, Gonzalez-Neira A, Ghoussaini M, Dennis J, Milne RL, et al. Large-scale genotyping identifies 41 new loci associated with breast cancer risk. Nat Genet. 2013;45: 353–361, 361e351–352. 10.1038/ng.2563 PubMed DOI PMC

Eeles RA, Olama AA, Benlloch S, Saunders EJ, Leongamornlert DA, Tymrakiewicz M, et al. Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array. Nat Genet. 2013;45: 385–391, 391e381–382. 10.1038/ng.2560 PubMed DOI PMC

Pharoah PD, Tsai YY, Ramus SJ, Phelan CM, Goode EL, Lawrenson K, et al. GWAS meta-analysis and replication identifies three new susceptibility loci for ovarian cancer. Nat Genet. 2013;45: 362–370, 370e361–362. 10.1038/ng.2564 PubMed DOI PMC

Antoniou AC, Wang X, Fredericksen ZS, McGuffog L, Tarrell R, Sinilnikova OM, et al. A locus on 19p13 modifies risk of breast cancer in BRCA1 mutation carriers and is associated with hormone receptor-negative breast cancer in the general population. Nat Genet. 2010;42: 885–892. 10.1038/ng.669 PubMed DOI PMC

Gold B, Kirchhoff T, Stefanov S, Lautenberger J, Viale A, Garber J, et al. Genome-wide association study provides evidence for a breast cancer risk locus at 6q22.33. Proc Natl Acad Sci U S A. 2008;105: 4340–4345. 10.1073/pnas.0800441105 PubMed DOI PMC

Barnes DR, Lee A, Easton DF, Antoniou AC Evaluation of association methods for analysing modifiers of disease risk in carriers of high-risk mutations. Genet Epidemiol. 2012;36: 274–291. 10.1002/gepi.21620 PubMed DOI

Abecasis GR, Auton A, Brooks LD, DePristo MA, Durbin RM, Handsaker RE, et al. An integrated map of genetic variation from 1,092 human genomes. Nature. 2012;491: 56–65. 10.1038/nature11632 PubMed DOI PMC

Howie B, Marchini J, Stephens M Genotype imputation with thousands of genomes. G3 (Bethesda). 2011;1: 457–470. 10.1534/g3.111.001198 PubMed DOI PMC

Long JC, Williams RC, Urbanek M An E-M algorithm and testing strategy for multiple-locus haplotypes. Am J Hum Genet. 1995;56: 799–810. PubMed PMC

van de Vijver MJ, He YD, van't Veer LJ, Dai H, Hart AA, Voskuil DW, et al. A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med. 2002;347: 1999–2009. PubMed

Chang HY, Nuyten DS, Sneddon JB, Hastie T, Tibshirani R, Sorlie T, et al. Robustness, scalability, and integration of a wound-response gene expression signature in predicting breast cancer survival. Proc Natl Acad Sci U S A. 2005;102: 3738–3743. PubMed PMC

Rhie SK, Coetzee SG, Noushmehr H, Yan C, Kim JM, Haiman CA, et al. Comprehensive functional annotation of seventy-one breast cancer risk Loci. PLoS One. 2013;8: e63925 10.1371/journal.pone.0063925 PubMed DOI PMC

Trapnell C, Pachter L, Salzberg SL TopHat: discovering splice junctions with RNA-Seq. Bioinformatics. 2009;25: 1105–1111. 10.1093/bioinformatics/btp120 PubMed DOI PMC

Heinz S, Benner C, Spann N, Bertolino E, Lin YC, Laslo P, et al. Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities. Mol Cell. 2010;38: 576–589. 10.1016/j.molcel.2010.05.004 PubMed DOI PMC

Quinlan AR, Hall IM BEDTools: a flexible suite of utilities for comparing genomic features. Bioinformatics. 2010;26: 841–842. 10.1093/bioinformatics/btq033 PubMed DOI PMC

Zhang Y, Liu T, Meyer CA, Eeckhoute J, Johnson DS, Bernstein BE, et al. Model-based analysis of ChIP-Seq (MACS). Genome Biol. 2008;9: R137 10.1186/gb-2008-9-9-r137 PubMed DOI PMC

Zhu LJ, Gazin C, Lawson ND, Pages H, Lin SM, Lapointe DS, et al. ChIPpeakAnno: a Bioconductor package to annotate ChIP-seq and ChIP-chip data. BMC Bioinformatics. 2010;11: 237 10.1186/1471-2105-11-237 PubMed DOI PMC

ENCODE An integrated encyclopedia of DNA elements in the human genome. Nature. 2012;489: 57–74. 10.1038/nature11247 PubMed DOI PMC

Douzery EJ, Scornavacca C, Romiguier J, Belkhir K, Galtier N, Delsuc F, et al. OrthoMaM v8: a database of orthologous exons and coding sequences for comparative genomics in mammals. Mol Biol Evol. 2014;31: 1923–1928. 10.1093/molbev/msu132 PubMed DOI

Loytynoja A, Goldman N Phylogeny-aware gap placement prevents errors in sequence alignment and evolutionary analysis. Science. 2008;320: 1632–1635. 10.1126/science.1158395 PubMed DOI

Yang Z PAML 4: phylogenetic analysis by maximum likelihood. Mol Biol Evol. 2007;24: 1586–1591. PubMed

Swanson WJ, Nielsen R, Yang Q Pervasive adaptive evolution in mammalian fertilization proteins. Mol Biol Evol. 2003;20: 18–20. PubMed

Yang Z, Wong WS, Nielsen R Bayes empirical bayes inference of amino acid sites under positive selection. Mol Biol Evol. 2005;22: 1107–1118. PubMed

Sohr S, Engeland K RHAMM is differentially expressed in the cell cycle and downregulated by the tumor suppressor p53. Cell Cycle. 2008;7: 3448–3460. PubMed

Ross-Innes CS, Stark R, Teschendorff AE, Holmes KA, Ali HR, Dunning MJ, et al. Differential oestrogen receptor binding is associated with clinical outcome in breast cancer. Nature. 2012;481: 389–393. 10.1038/nature10730 PubMed DOI PMC

Corona E, Dudley JT, Butte AJ Extreme evolutionary disparities seen in positive selection across seven complex diseases. PLoS One. 2010;5: e12236 10.1371/journal.pone.0012236 PubMed DOI PMC

Keane M, Craig T, Alfoldi J, Berlin AM, Johnson J, Seluanov A, et al. The Naked Mole Rat Genome Resource: facilitating analyses of cancer and longevity-related adaptations. Bioinformatics. 2014;30: 3558–3560. 10.1093/bioinformatics/btu579 PubMed DOI PMC

Hill SJ, Rolland T, Adelmant G, Xia X, Owen MS, Dricot A, et al. Systematic screening reveals a role for BRCA1 in the response to transcription-associated DNA damage. Genes Dev. 2014;28: 1957–1975. 10.1101/gad.241620.114 PubMed DOI PMC

Drees BL, Thorsson V, Carter GW, Rives AW, Raymond MZ, Avila-Campillo I, et al. Derivation of genetic interaction networks from quantitative phenotype data. Genome Biol. 2005;6: R38 PubMed PMC

Fletcher O, Johnson N, Palles C, dos Santos Silva I, McCormack V, Whittaker J, et al. Inconsistent association between the STK15 F31I genetic polymorphism and breast cancer risk. J Natl Cancer Inst. 2006;98: 1014–1018. PubMed

Shi H, Bevier M, Johansson R, Grzybowska E, Chen B, Eyfjord JE, et al. Single nucleotide polymorphisms in the 20q13 amplicon genes in relation to breast cancer risk and clinical outcome. Breast Cancer Res Treat. 2011;130: 905–916. 10.1007/s10549-011-1600-5 PubMed DOI