The CHEK2*1100de/C allelic variant and risk of breast cancer:: Screening results from the breast cancer family registry
The CHEK2*1100de/C allelic variant and risk of breast cancer:: Screening results from the breast cancer family registry
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DOI：
10.1158/1055-9965.epi-05-0557
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发表时间：
2006-02-01
影响因子：
3.8
通讯作者：
Concannon, P
中科院分区：
文献类型：
--
作者：
Bernstein, JL;Teraoka, SN;Concannon, P
CHEK 2是一种丝氨酸-苏氨酸激酶，响应于诱导DNA双链断裂的试剂（如电离辐射）而被激活。CHEK 2的激活可导致细胞周期检查点停滞或细胞凋亡。一种特异性变异CHEK 2 * 1100 delC与乳腺癌风险增加有关。在这项基于人群的研究中，我们筛选了2,311例女性乳腺癌病例和496例一般人群对照，这些病例和对照都是在安大略和北方加州乳腺癌家族登记处登记的（所有对照都是加拿大人）。总体而言，30例病例和1例对照携带1100 delC等位基因。在安大略，病例组和对照组的加权突变携带者频率分别为1.34%和0.20%[比值比（OR），6.65; 95%置信区间（95%CI），2.37-18.681]。在加州，病例中的加权群体突变携带者频率为0.40%。在所有病例中，524名非白种人中有1名（0.19%）和1，775名白种人中有29名（1.63%）为突变携带者（OR，0.12; 95% CI，0.02-0.89）。在诊断时年龄> 45岁的白人病例中，携带者状态与良性乳腺疾病史相关（OR，3.18; 95% CI，1.30-7.80）和诊断电离辐射暴露（排除乳腺X线摄影; OR，3.21; 95% CI，1.13-9.14）;与未暴露于电离辐射的女性相比，在诊断前暴露于电离辐射> 15年的女性中，这种关联最强两次或两次以上胸部X线检查者OR为3.63（95% CI为1.25-10.52）。支持CHEK 2在乳腺癌发生中的生物学相关性的这些数据表明，可能需要进一步研究CHEK 2 * 1100 delC载体状态和辐射暴露的联合作用。
CHEK2, a serine-threonine kinase, is activated in response to agents, such as ionizing radiation, which induce DNA double-strand breaks. Activation of CHEK2 can result in cell cycle checkpoint arrest or apoptosis. One specific variant, CHEK2*1100delC, has been associated with an increased risk of breast cancer. In this population-based study, we screened 2,311 female breast cancer cases and 496 general population controls enrolled in the Ontario and Northern California Breast Cancer Family Registries for this variant (all controls were Canadian). Overall, 30 cases and one control carried the 1100delC allele. In Ontario, the weighted mutation carrier frequency among cases and controls was 1.34% and 0.20%, respectively [odds ratio (OR), 6.65; 95% confidence interval (95% CI), 2.37-18.681. In California, the weighted population mutation carrier frequency in cases was 0.40%. Across all cases, 1 of 524 non-Caucasians (0.19%) and 29 of 1,775 Caucasians (1.63%) were mutation carriers (OR, 0.12; 95% Cl, 0.02-0.89). Among Caucasian cases > 45 years age at diagnosis, carrier status was associated with history of benign breast disease (OR, 3.18; 95% Cl, 1.30-7.80) and exposure to diagnostic ionizing radiation (excluding mammography; OR, 3.21; 95% Cl, 1.13-9.14); compared with women without exposure to ionizing radiation, the association was strongest among women exposed > 15 years before diagnosis (OR, 4.28; 95% CI, 1.50-12.20) and among those who received two or more chest X-rays (OR, 3.63; 95% Cl, 1.25-10.52). These data supporting the biological relevance of CHEK2 in breast carcinogenesis suggest that further studies examining the joint roles of CHEK2*1100delC carrier status and radiation exposure may be warranted.