在乳腺癌病例中对复发性DNA损伤反应基因变异进行基于人口的研究
Anna Tervasmäki1,2, Timo A Kumpula1,2, Mervi Grip3
1Laboratory of Cancer Genetics and Tumor Biology, Translational Medicine Research Unit, University of Oulu, Aapistie 5A, 90220, Oulu, Finland.
Breast cancer research and treatment
|February 26, 2025
概括
北芬兰对DNA损伤反应 (DDR) 基因变异的基因测试确定了BRCA1/2和PALB2等高风险等位基因,有助于乳腺癌诊断和治疗决策.
科学领域:
- 遗传学和基因组学 遗传学和基因组学
- 在瘤学瘤学.
- 分子生物学分子生物学
背景情况:
- DNA损伤反应 (DDR) 基因的生殖系变异与乳腺癌风险增加有关.
- 以前的研究表明,芬兰北部人口中某些DDR基因变异的丰富.
研究的目的:
- 改进北芬兰16种复发性致病性/可能致病性DDR基因变异的种群患病率和风险估计.
- 研究这些变体与乳腺癌风险和瘤特征的关联.
主要方法:
- 在2343个未经选择的芬兰北部乳腺癌病例和4607个无癌症对照中,对16种DDR基因变异进行基因定型.
- 分析瘤特征 (等级,受体状况,多焦点性) 和变异载体癌症家族史.
主要成果:
- 确认BRCA1,BRCA2,PALB2 c.1592delT和ATM c.7570G>C变体是高风险等位基因.
- 鉴定出CHEK2 c.1100delC,MCPH1 c.909_921del和RAD50 c.687delT变体是中等风险的等位基因.
- 致病变体的双载体具有显著更高的乳腺癌风险 (OR 7.2);特定变体与瘤等级,受体状态和多焦点性相关.
结论:
- 研究的DDR基因变异在9%的未经选择的乳腺癌病例中被发现.
- 在DDR基因中的生殖系致病变体为手术和瘤治疗决策提供了有价值的信息.
- 对DDR变异的基因测试应被视为乳腺癌诊断的组成部分.
相关概念视频
Nucleotide Excision Repair
3.4K
DNA Distortion and Damage
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
3.4K
Base-pairing and DNA Repair
64.5K
64.5K
Genome-wide Association Studies-GWAS
12.3K
Genome-wide association studies or GWAS are used to identify whether common SNPs are associated with certain diseases. Suppose specific SNPs are more frequently observed in individuals with a particular disease than those without the disease. In that case, those SNPs are said to be associated with the disease. Chi-square analysis is performed to check the probability of the allele likely to be associated with the disease.
GWAS does not require the identification of the target gene involved in...
GWAS does not require the identification of the target gene involved in...
12.3K
Base Excision Repair
21.8K
One of the common DNA damages is the chemical alteration of single bases by alkylation, oxidation, or deamination. The altered bases cause mispairing and strand breakage during replication. This type of damage causes minimal change to the DNA double helix structure and can be repaired by the base excision repair (BER) pathways. BER corrects damaged DNA sequences by removing the damaged base and restoring the original base sequence using the complementary strand as a template.
The first step of...
The first step of...
21.8K
DNA Damage can Stall the Cell Cycle
9.0K
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
9.0K
Overview of DNA Repair
7.4K
7.4K


