Risk, Prediction and Prevention of Hereditary Breast Cancer – Large-Scale Genomic Studies in Times of Big and Smart Data

Marius Wunderle; Gregor Olmes; Naiba Nabieva; Lothar Häberle; Sebastian M. Jud; Alexander Hein; Claudia Rauh; Carolin C. Hack; Ramona Erber; Arif B. Ekici; Juliane Hoyer; Georgia Vasileiou; Cornelia Kraus; André Reis; Arndt Hartmann; Rüdiger Schulz-Wendtland; Michael P. Lux; Matthias W. Beckmann; Peter A. Fasching

doi:10.1055/a-0603-4350

Geburtshilfe und Frauenheilkunde, Inhaltsverzeichnis

CC BY-NC-ND 4.0 · Geburtshilfe Frauenheilkd 2018; 78(05): 481-492
DOI: 10.1055/a-0603-4350

GebFra Science

Review

Georg Thieme Verlag KG Stuttgart · New York

Risk, Prediction and Prevention of Hereditary Breast Cancer – Large-Scale Genomic Studies in Times of Big and Smart Data

Risiko, Vorhersage und Prävention von erblichem Brustkrebs – groß angelegte genomische Studien in Zeiten von Big und Smart Data

Marius Wunderle

¹Department of Gynecology and Obstetrics, University Hospital Erlangen, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany

,

Gregor Olmes

¹Department of Gynecology and Obstetrics, University Hospital Erlangen, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany

,

Naiba Nabieva

¹Department of Gynecology and Obstetrics, University Hospital Erlangen, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany

,

Lothar Häberle

¹Department of Gynecology and Obstetrics, University Hospital Erlangen, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany

²Biostatistics Unit, Department of Gynecology and Obstetrics, Erlangen University Hospital, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany

,

Sebastian M. Jud

¹Department of Gynecology and Obstetrics, University Hospital Erlangen, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany

,

Alexander Hein

¹Department of Gynecology and Obstetrics, University Hospital Erlangen, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany

,

Claudia Rauh

¹Department of Gynecology and Obstetrics, University Hospital Erlangen, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany

,

Carolin C. Hack

¹Department of Gynecology and Obstetrics, University Hospital Erlangen, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany

,

Ramona Erber

³Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany

,

Arif B. Ekici

⁴Institute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany

,

Juliane Hoyer

⁴Institute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany

,

Georgia Vasileiou

⁴Institute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany

,

Cornelia Kraus

⁴Institute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany

,

André Reis

⁴Institute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany

,

Arndt Hartmann

³Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany

,

Rüdiger Schulz-Wendtland

⁵Institute of Diagnostic Radiology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany

,

Michael P. Lux

¹Department of Gynecology and Obstetrics, University Hospital Erlangen, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany

,

Matthias W. Beckmann

¹Department of Gynecology and Obstetrics, University Hospital Erlangen, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany

,

Peter A. Fasching

¹Department of Gynecology and Obstetrics, University Hospital Erlangen, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany

› Institutsangaben

Abstract

Over the last two decades genetic testing for mutations in BRCA1 and BRCA2 has become standard of care for women and men who are at familial risk for breast or ovarian cancer. Currently, genetic testing more often also includes so-called panel genes, which are assumed to be moderate-risk genes for breast cancer. Recently, new large-scale studies provided more information about the risk estimation of those genes. The utilization of information on panel genes with regard to their association with the individual breast cancer risk might become part of future clinical practice. Furthermore, large efforts have been made to understand the influence of common genetic variants with a low impact on breast cancer risk. For this purpose, almost 450 000 individuals have been genotyped for almost 500 000 genetic variants in the OncoArray project. Based on first results it can be assumed that – together with previously identified common variants – more than 170 breast cancer risk single nucleotide polymorphisms can explain up to 18% of familial breast cancer risk. The knowledge about genetic and non-genetic risk factors and its implementation in clinical practice could especially be of use for individualized prevention. This includes an individualized risk prediction as well as the individualized selection of screening methods regarding imaging and possible lifestyle interventions. The aim of this review is to summarize the most recent developments in this area and to provide an overview on breast cancer risk genes, risk prediction models and their utilization for the individual patient.

Zusammenfassung

In den letzten 2 Jahrzehnten wurden genetische Testungen zur Erkennung von BRCA1- und BRCA2-Mutationen Teil der Standardversorgung für Personen mit einem erhöhten familiären Risiko, an Brust- oder Eierstockkrebs zu erkranken. Zurzeit wird bei genetischen Testungen immer öfters auch nach Mutationen in sogenannten Panel-Genen gesucht, von denen angenommen wird, dass sie mit einem mittleren Erkrankungsrisiko für Brustkrebs einhergehen. Vor Kurzem wurden die Ergebnisse neuer großangelegter Studien publiziert, die mehr Informationen über die Risikoabschätzung für diese Gene bieten. Die Nutzung dieses neuen Wissens über Panel-Gene und des damit verbundenen individuellen Erkrankungsrisikos könnte in Zukunft klinischer Alltag sein. Dazu kommt, dass auch große Anstrengungen unternommen wurden, um den Einfluss häufig vorkommender genetischer Varianten, die nur geringe Auswirkungen auf das Brustkrebsrisiko haben, zu verstehen. Zu diesem Zwecke wurde im Zuge des OncoArray-Projekts eine Genotypisierung von annähernd 500 000 genetischen Varianten bei fast 450 000 Personen vorgenommen. Basierend auf den ersten Zwischenergebnissen wird nun angenommen, dass es zusammen mit den bereits zuvor identifizierten häufig vorkommenden Varianten mehr als 170 Einzelnukleotid-Polymorphismen gibt, die ein Brustkrebsrisiko bergen und die bis zu 18% des familiären Risikos, an Brustkrebs zu erkranken, erklären können. Die Umsetzung des Wissens von genetischen und nicht genetischen Risikofaktoren in die klinische Praxis könnte besonders für individuelle Präventionsmaßnahmen von Nutzen sein. Hierzu zählen sowohl die individuelle Risikovorhersage, die individualisierte Auswahl von bildgebenden Verfahren für Vorsorgeuntersuchungen sowie potenzielle Lebensstil-Interventionen. Ziel dieses Artikels ist es, die neuesten Entwicklungen auf diesem Gebiet zusammenzufassen sowie einen Überblick über Brustkrebsrisikogene, Risikovorhersagemodelle und deren Nutzen für individuelle Patientinnen zu geben.

Key words

breast cancer - risk - BRCA1 - BRCA2 - panel genes - SNP

Schlüsselwörter

Brustkrebs - Risiko - BRCA1 - BRCA2 - Panel-Gene - SNP - Einzelnukleotid-Polymorphismen

Volltext

Referenzen

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