Age- and tumor subtype-specific breast cancer risk estimates for CHEK2*1100delC carriers
Schmidt, Marjanka K Hogervorst, Frans van, Hien Richard Cornelissen, Sten Broeks, Annegien Adank, Muriel Meijers, Hanne Waisfisz, Quinten Hollestelle, Antoinette Schutte, Mieke
Schmidt, Marjanka K
Hogervorst, Frans
van, Hien Richard
Cornelissen, Sten
Broeks, Annegien
Adank, Muriel
Meijers, Hanne
Waisfisz, Quinten
Hollestelle, Antoinette
Schutte, Mieke
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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.
Date
2016
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Publisher
American Society of Clinical Oncology