Age- and Tumor Subtype Specific Breast Cancer Risk Estimates for CHEK2*1100delC Carriers

作者：Schmidt Marjanka K^*; Hogervorst Frans; van Hien Richard; Cornelissen Sten; Broeks Annegien; Adank Muriel A; 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 C; Arndt Volker; Bermisheva Marina; Bogdanova Natalia V; Bolla Manjeet K; Brauch Hiltrud; Brenner Hermann; Bruning Thomas; Burwinkel Barbara; Chang Claude Jenny

来源：Journal of Clinical Oncology, 2016, 34(23): 2750-+.

DOI：10.1200/JCO.2016.66.5844

Purpose
CHEK2*1100delC is a well-established breast cancer risk variant that is most prevalent in European populations; however, there are limited data on risk of breast cancer by age and tumor subtype, which limits its usefulness in breast cancer risk prediction. We aimed to generate tumor subtype and age-specific risk estimates by using data from the Breast Cancer Association Consortium, including 44,777 patients with breast cancer and 42,997 controls from 33 studies genotyped for CHEK2*1100delC.
Patients and Methods
CHEK71100delC genotyping was mostly done by a custom Taqman assay. Breast cancer odds ratios (ORs) for CHEK71100delC carriers versus noncarriers were estimated by using logistic regression and adjusted for study (categorical) and age. Main analyses included patients with invasive breast cancer from population- and hospital-based studies.
Results
Proportions of heterozygous CHEK2*1100delC carriers in controls, in patients with breast cancer from population- and hospital-based studies, and in patients with breast cancer from familial- and clinical genetics center based studies were 0.5%, 1.3%, and 3.0%, respectively. The estimated OR for invasive breast cancer was 2.26 (95%CI, 1.90 to 2.69; P = 2.3 x 10(-20)). The OR was higher for estrogen receptor (ER) positive disease (2.55 [95%CI, 2.10 to 3.10; P = 4.9 x 10(-21)]) than it was for ER-negative disease (1.32 [95%CI, 0.93 to 1.88; P = .12]; P interaction = 9.9 x 10(-4)). The OR significantly declined with attained age for breast cancer overall (P = .001) and for ER-positive tumors (P = .001). Estimated cumulative risks for development of ER-positive and ER-negative tumors by age 80 in CHEK2*1100delC carriers were 20% and 3%, respectively, compared with 9% and 2%, respectively, in the general population of the United Kingdom.
Conclusion
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. J Clin Oncol 34:2750-2760.

• 出版日期2016-8-10