Górski B, Cybulski C, Huzarski T, Byrski T, Gronwald J, Jakubowska A, Stawicka M, Gozdecka-Grodecka S, Szwiec M, Urbański K, Mituś J, Marczyk E, Dziuba J, Wandzel P, Surdyka D, Haus O, Janiszewska H, Debniak T, Tołoczko-Grabarek A, Medrek K, Masojć B, Mierzejewski M, Kowalska E, Narod S A, Lubiński J
Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Polabska 4, Szczecin, Poland 70-115.
Breast Cancer Res Treat. 2005 Jul;92(1):19-24. doi: 10.1007/s10549-005-1409-1.
Mutant alleles of several genes in the DNA repair pathway have been found to predispose women to breast cancer. From a public health perspective, the importance of a given allele in a population is determined by the frequency of the allele and by the relative risk of breast cancer that it confers. In Poland founder alleles of the BRCA1, CHEK2 and NBS1 genes have been associated with an increased risk of breast cancer, but the relative contribution of each of these alleles to the overall breast cancer burden has not yet been determined. We screened 2012 unselected cases of breast cancer and 4000 population controls for 7 different mutations in these genes. Overall, a mutation was found in 12% of the cases and in 6% of the controls. Mutations in BRCA1 and CHEK2 contributed in approximately equal measure to the burden of breast cancer in Poland. A BRCA1 mutation was present in 3% of the cases. The missense BRCA1 mutation C61G was associated with a higher odds ratio for breast cancer (OR=15) than were either of the truncating BRCA1 mutations 4153delA (OR=2.0) and 5382insC (OR=6.2). In contrast, a higher odds ratio was seen for truncating CHEK2 mutations (OR=2.1) than for the missense mutation I157T (OR=1.4). This study suggests that cancer risks may be specific for particular alleles of a susceptibility gene and that these different risks should be taken into account by genetic counselors.
人们发现，DNA修复途径中多个基因的突变等位基因会使女性易患乳腺癌。从公共卫生的角度来看，某一等位基因在人群中的重要性由该等位基因的频率及其赋予的患乳腺癌相对风险决定。在波兰，BRCA1、CHEK2和NBS1基因的始祖等位基因与乳腺癌风险增加有关，但这些等位基因对总体乳腺癌负担的相对贡献尚未确定。我们对2012例未经选择的乳腺癌病例和4000名人群对照进行了这些基因7种不同突变的筛查。总体而言，12%的病例和6%的对照中发现了突变。BRCA1和CHEK2的突变对波兰乳腺癌负担的贡献大致相当。3%的病例存在BRCA1突变。错义BRCA1突变C61G与乳腺癌的优势比更高（OR=15），高于截短型BRCA1突变4153delA（OR=2.0）和5382insC（OR=6.2）中的任何一个。相比之下，截短型CHEK2突变的优势比（OR=2.1）高于错义突变I157T（OR=1.4）。这项研究表明，癌症风险可能因易感基因的特定等位基因而异，遗传咨询师应考虑这些不同的风险。
