Genetic modifiers of CHEK2*1100delC-associated breast cancer risk

Beitrag in einer Fachzeitschrift


Details zur Publikation

Autorinnen und Autoren: Muranen TA, Greco D, Blomqvist C, Aittomaki K, Khan S, Hogervorst F, Verhoef S, Pharoah PDP, Dunning AM, Shah M, Luben R, Bojesen SE, Nordestgaard BG, Schoemaker M, Swerdlow A, Garcia-Closas M, Figueroa J, Doerk T, Bogdanova NV, Hall P, Li J, Khusnutdinova E, Bermisheva M, Kristensen V, Borresen-Dale AL, Peto J, Silva IDS, Couch FJ, Olson JE, Hillemans P, Park-Simon TW, Brauch H, Hamann U, Burwinkel B, Marme F, Meindl A, Schmutzler RK, Cox A, Cross SS, Sawyer EJ, Tomlinson I, Lambrechts D, Moisse M, Lindblom A, Margolin S, Hollestelle A, Martens JWM, Fasching P, Beckmann M, Andrulis IL, Knight JA, Anton-Culver H, Ziogas A, Giles GG, Milne RL, Brenner H, Arndt V, Mannermaa A, Kosma VM, Chang-Claude J, Rudolph A, Devilee P, Seynaeve C, Hopper JL, Southey MC, John EM, Whittemore AS, Bolla MK, Wang Q, Michailidou K, Dennis J, Easton DF, Schmidt MK, Nevanlinna H
Zeitschrift: Genetics in Medicine
Jahr der Veröffentlichung: 2017
Band: 19
Heftnummer: 5
Seitenbereich: 599-603
ISSN: 1098-3600


Abstract

PURPOSE: CHEK2*1100delC is a founder variant in European populations that confers a two- to threefold increased risk of breast cancer (BC). Epidemiologic and family studies have suggested that the risk associated with CHEK2*1100delC is modified by other genetic factors in a multiplicative fashion. We have investigated this empirically using data from the Breast Cancer Association Consortium (BCAC).
METHODS: Using genotype data from 39,139 (624 1100delC carriers) BC patients and 40,063 (224) healthy controls from 32 BCAC studies, we analyzed the combined risk effects of CHEK2*1100delC and 77 common variants in terms of a polygenic risk score (PRS) and pairwise interaction.
RESULTS: The PRS conferred odds ratios (OR) of 1.59 (95% CI: 1.21-2.09) per standard deviation for BC for CHEK2*1100delC carriers and 1.58 (1.55-1.62) for noncarriers. No evidence of deviation from the multiplicative model was found. The OR for the highest quintile of the PRS was 2.03 (0.86-4.78) for CHEK2*1100delC carriers, placing them in the high risk category according to UK NICE guidelines. The OR for the lowest quintile was 0.52 (0.16-1.74), indicating a lifetime risk close to the population average.
CONCLUSION: Our results confirm the multiplicative nature of risk effects conferred by CHEK2*1100delC and the common susceptibility variants. Furthermore, the PRS could identify carriers at a high lifetime risk for clinical actions.Genet Med advance online publication 06 October 2016.


FAU-Autorinnen und Autoren / FAU-Herausgeberinnen und Herausgeber

Beckmann, Matthias Prof. Dr.
Lehrstuhl für Geburtshilfe und Frauenheilkunde
Fasching, Peter PD Dr.
Professur für Translationale Frauenheilkunde und Geburtshilfe


Einrichtungen weiterer Autorinnen und Autoren

Antoni van Leeuwenhoek
Bashkir State University / Башкирский государственный университет
Cancer Prevention Institute of California (CPIC)
Deutsches Krebsforschungszentrum (DKFZ)
Erasmus University Medical Center
Finnish Institute of Occupational Health (FIOH) / Työterveyslaitos (TTL)
Helsingin yliopisto / University of Helsinki
Karolinska Institute
Katholieke Universiteit Leuven (KUL) / Catholic University of Leuven
King’s College London
Leiden University
London School of Hygiene and Tropical Medicine
Mayo Clinic
Medizinische Hochschule Hannover (MHH) / Hannover Medical School
National Cancer Institute (NCI)
Ruprecht-Karls-Universität Heidelberg
Stanford University
Technische Universität München (TUM)
The Institute of Cancer Research (ICR)
The University of Melbourne
Universität Köln
University of California Irvine
University of Cambridge
University of Copenhagen
University of Eastern Finland
University of Oslo
University of Oxford
University of Sheffield
University of Toronto


Zitierweisen

APA:
Muranen, T.A., Greco, D., Blomqvist, C., Aittomaki, K., Khan, S., Hogervorst, F.,... Nevanlinna, H. (2017). Genetic modifiers of CHEK2*1100delC-associated breast cancer risk. Genetics in Medicine, 19(5), 599-603. https://dx.doi.org/10.1038/gim.2016.147

MLA:
Muranen, Taru A., et al. "Genetic modifiers of CHEK2*1100delC-associated breast cancer risk." Genetics in Medicine 19.5 (2017): 599-603.

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Zuletzt aktualisiert 2019-28-03 um 08:53