Age- and Tumor Subtype Specific Breast Cancer Risk Estimates for CHEK2*1100delC Carriers
Age- and Tumor Subtype Specific Breast Cancer Risk Estimates for CHEK2*1100delC Carriers
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DOI：
10.1200/jco.2016.66.5844
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发表时间：
2016-08-10
影响因子：
45.3
通讯作者：
Easton, Douglas F.
中科院分区：
文献类型：
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作者：
Schmidt, Marjanka K.;Hogervorst, Frans;Easton, Douglas F.
CHEK 2 * 1100 delC是一种在欧洲人群中最常见的乳腺癌风险变异;然而，关于年龄和肿瘤亚型的乳腺癌风险的数据有限，这限制了其在乳腺癌风险预测中的有用性。我们的目的是通过使用来自乳腺癌协会的数据来产生肿瘤亚型和年龄特异性风险估计，包括来自33项研究的44，777名乳腺癌患者和42，997名对照CHEK 2 * 1100 delC基因分型。CHEK 71100 delC携带者与非携带者的乳腺癌优势比（OR）通过使用逻辑回归进行估计，并针对研究（分类）和年龄进行调整。主要分析包括浸润性乳腺癌患者从人口和医院为基础的study. ResultsCHEK 2 * 1100 delC杂合载体在对照组中的比例，在乳腺癌患者从人口和医院为基础的研究，并在乳腺癌患者从家族和临床遗传学中心为基础的研究分别为0.5%，1.3%，和3.0%，分别。浸润性乳腺癌的估计OR为2.26（95%CI，1.90 - 2.69; P = 2.3 x 10（-20））。雌激素受体（ER）阳性疾病的OR（2.55 [95%CI，2.10 - 3.10; P = 4.9 x 10（-21）]）高于ER阴性疾病的OR（1.32 [95%CI，0.93 - 1.88; P = 0.12]; P相互作用= 9.9 x 10（-4））。总体乳腺癌（P = 0.001）和ER阳性肿瘤（P = 0.001）的OR随年龄增长而显著下降。在CHEK 2 * 1100 delC携带者中，到80岁时发生ER阳性和ER阴性肿瘤的估计累积风险分别为20%和3%，相比之下，分别为9%和2%，结论这些CHEK 2 * 1100 delC乳腺癌风险估计为纳入CHEK 2 * 1100 delC纳入乳腺癌风险预测模型，并纳入强化筛查和随访指南。临床肿瘤学杂志34：2750-2760。(C)2016年美国临床肿瘤学会
PurposeCHEK2*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 MethodsCHEK71100delC 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.ResultsProportions 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.ConclusionThese 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. (C) 2016 by American Society of Clinical Oncology