Serrano-Fernández Pablo, Debniak Tadeusz, Górski Bohdan, Bogdanova Natalia, Dörk Thilo, Cybulski Cezary, Huzarski Tomasz, Byrski Tomasz, Gronwald Jacek, Wokołorczyk Dominika, Narod Steven A, Lubiński Jan
International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
Breast Cancer Res Treat. 2009 Sep;117(1):161-5. doi: 10.1007/s10549-008-0249-1. Epub 2008 Nov 22.
We studied the effects of BRCA2 and CHEK2 variants on breast cancer risk in two case-control series from Poland and Belarus. The missense BRCA2 variant T1915M was associated with a significant reduction in breast cancer risk (OR = 0.62; 95% CI 0.49-0.79; P = 0.0007). Modest increases of breast cancer risk were observed for the four analysed CHEK2 variants (I157T, 1100delC, IVS2 + 1G > A and del5395) (OR = 2.2; 95% 1.7-2.8; P = 0.0001). The highest risk was observed among women who carried both a BRCA2 and a CHEK2 variant (OR = 5.7; 95% CI 1.7-19; P = 0.006). We observed a statistically significant interaction effect between CHEK2 mutations and the BRCA2 substitution (P = 0.03). These data suggest that the BRCA2 T1915M polymorphism alone might be associated with a reduced risk of breast cancer, but among CHEK2 mutation carriers, it may lead to an unexpectedly high risk.
我们在来自波兰和白俄罗斯的两个病例对照系列研究中，探讨了BRCA2和CHEK2基因变异对乳腺癌风险的影响。错义BRCA2基因变异T1915M与乳腺癌风险显著降低相关（比值比[OR]=0.62；95%置信区间[CI]为0.49-0.79；P=0.0007）。对于分析的四种CHEK2基因变异（I157T、1100delC、IVS2+1G>A和del5395），观察到乳腺癌风险有适度增加（OR=2.2；95%CI为1.7-2.8；P=0.0001）。在同时携带BRCA2和CHEK2基因变异的女性中观察到最高风险（OR=5.7；95%CI为1.7-19；P=0.006）。我们观察到CHEK2基因突变与BRCA2基因替代之间存在统计学显著的交互作用（P=0.03）。这些数据表明，单独的BRCA2基因T1915M多态性可能与乳腺癌风险降低相关，但在CHEK2基因突变携带者中，它可能导致出乎意料的高风险。
