Publication:
Age- and tumor subtype-specific breast cancer risk estimates for CHEK2*1100delC carriers

Date
2016
Authors
Schmidt, Marjanka K
Hogervorst, Frans
van, Hien Richard
Cornelissen, Sten
Broeks, Annegien
Adank, Muriel
Meijers, Hanne
Waisfisz, Quinten
Hollestelle, Antoinette
Schutte, Mieke
van, den Ouweland Ans
Hooning, Maartje
Andrulis, Irene L
Anton-Culver, Hoda
Antonenkova, Natalia N
Antoniou, Antonis
Arndt, Volker
Bermisheva, Marina
Bogdanova, Natalia V
Bolla, Manjeet K
Brauch, Hiltrud
Brenner, Hermann
Br├╝ning, Thomas
Burwinkel, Barbara
Chang-Claude, Jenny
Chenevix-Trench, Georgia
Couch, Fergus J
Cox, Angela
Cross, Simon S
Czene, Kamila
Dunning, Alison
Fasching, Peter A
Figueroa, Jonine
Fletcher, Olivia
Flyger, Henrik
Galle, Eva
García-Closas, Montserrat
Giles, Graham G
Haeberle, Lothar
Hall, Per
Hillemanns, Peter
Hopper, John L
Jakubowska, Anna
John, Esther M
Jones, Michael
Khusnutdinova, Elza
Knight, Julia A
Kosma, Veli-Matti
Kristensen, Vessela
Lee, Andrew
Lindblom, Annika
Lubinski, Jan
Mannermaa, Arto
Margolin, Sara
Meindl, Alfons
Milne, Roger L
Muranen, Taru A
NBCS, Investigators
Newcomb, Polly A
Offitt, Kenneth
Park-Simon, Tjoung-Won
Peto, Julian
Pharoah, Paul
Robson, Mark
Rudolph, Anja
Sawyer, Elinor J
Schmutzler, Rita K
Seynaeve, Caroline
Soens, Julie
Southey, Melissa C
Spurdle, Amanda
Surowy, Harald
Swerdlow, Anthony
Tollenaar, Rob AEM
Tomlinson, Ian
Trentham-Dietz, Amy
Vachon, Celine
Wang, Qin
Whittemore, Alice S
Ziogas, Argyrios
van, der Kolk Lizet
Nevanlinna, Heli
D├╢rk, Thilo
Bojesen, Stig
Easton, Douglas
Journal Title
Journal ISSN
Volume Title
Publisher
American Society of Clinical Oncology
Authors
Schmidt, Marjanka K
Hogervorst, Frans
van, Hien Richard
Cornelissen, Sten
Broeks, Annegien
Adank, Muriel
Meijers, Hanne
Waisfisz, Quinten
Hollestelle, Antoinette
Schutte, Mieke
Research Projects
Research Project
C1287/A10118
Research Project
HEALTH-F2-2009-223175
Research Project
CA192393
Organizational Units
Organizational Unit
Organizational Unit
Organizational Unit
Organizational Unit
Organizational Unit
Journal Issue
Abstract
Description
CHEK2*1100delC is a well-established breast cancer risk variant, most prevalent in European populations. However, there are limited data on risk of breast cancer by age and tumor subtype, limiting its usefulness in breast cancer risk prediction. We aimed to generate tumor subtype- and age-specific risk estimates using data from the Breast Cancer Association Consortium, including 44,777 breast cancer patients and 42,997 controls from 33 studies genotyped for CHEK2*1100delC. CHEK2*1100delC genotyping was mostly done by a custom Taqman assay. Breast cancer odds ratios (OR) for CHEK2*1100delC carriers versus non-carriers were estimated using logistic regression; adjusting for study (categorical) and age. Main analyses included invasive breast cancer patients from population- and hospital-based studies. The proportions of heterozygous CHEK2*1100delC carriers in controls, in breast cancer patients from population- and hospital-based studies, and in breast cancer patients from familial and clinical genetics center-based studies, were 0.5%, 1.3%, and 3.0% respectively. The estimated OR f or invasive breast cancer was 2.26 (95%CI:1.90-2.69; p=2.3x10^-20). The OR was higher f or estrogen receptor (ER)-positive disease 2.55 (95%CI:2.10-3.10; p=4.9x10^-21) than for ER-negative disease 1.32 (95%CI: 0.93-1.88; p=0.12) (p interaction=9.9x10^-4). The OR significantly declined with attained age for breast cancer overall (p=0.001) and for ER-positive tumors (p=0.001). Estimated cumulative risks for CHEK2*1100delC carriers for the development of ER-positive and ER-negative tumors by age 80 were respectively 20% and 3%, compared with 9% and 2% in the UK general population. These CHEK2*1100delC breast cancer risk estimates provide a basis for incorporating CHEK2*1100delC into breast cancer risk prediction models, and into guidelines for intensified screening and follow-up.
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