Map making in the 21st century: charting breast cancer susceptibility pathways in rodent models.
Map making in the 21st century: charting breast cancer susceptibility pathways in rodent models.
复制标题
DOI：
10.1007/s10911-011-9201-9
复制
发表时间：
2011-04
影响因子：
2.5
通讯作者：
Jerry DJ
中科院分区：
文献类型：
--
作者：
Blackburn AC;Jerry DJ
遗传因素在决定乳腺癌增加的风险和抵抗方面起着重要作用。最近的技术进步使在人类大规模关联研究中分析数十万个单核苷酸多态性成为可能，并在20多个影响乳腺癌风险的基因中确定了等位基因。尽管取得了这些进展，但挑战仍然在于确定哪些功能多态性会增加风险，以及这些遗传变异如何相互作用以及如何与环境因素相互作用。在啮齿类动物中，乳腺肿瘤的发病率因菌株而异，因此它们可以为涉及人类的候选途径提供替代思路。在动物身上进行的测绘研究已经发现了许多乳腺癌易感性的基因座，这些基因座已经在人类群体中得到了验证。以相互的方式，敲入和敲除小鼠已被用于验证在人群研究中发现的风险等位基因的致瘤性。啮齿类动物研究也强调了等位基因之间相互作用的复杂性。影响啮齿动物乳腺肿瘤风险和抗性的基因在很大程度上取决于致癌挑战，这一事实强调了基因与环境相互作用的重要性。啮齿类动物遗传学家现在面临的挑战是利用在啮齿动物肿瘤发生模型中控制遗传和环境的能力，更好地了解乳腺癌发展的生物学，确定与人类易感性最相关的多态性，并确定补偿途径，以改善患乳腺癌风险最高的妇女的预防。
Genetic factors play an important role in determining risk and resistance to increased breast cancer. Recent technological advances have made it possible to analyze hundreds of thousands of single nucleotide polymorphisms in large-scale association studies in humans and have resulted in identification of alleles in over 20 genes that influence breast cancer risk. Despite these advances, the challenge remains in identifying what the functional polymorphisms are that confer the increased risk, and how these genetic variants interact with each other and with environmental factors. In rodents, the incidence of mammary tumors varies among strains, such that they can provide alternate ideas for candidate pathways involved in humans. Mapping studies in animals have unearthed numerous loci for breast cancer susceptibility that have been validated in human populations. In a reciprocal manner, knockin and knockout mice have been used to validate the tumorigenicity of risk alleles found in population studies. Rodent studies also underscore the complexity of interactions among alleles. The fact that genes affecting risk and resistance to mammary tumors in rodents depend greatly upon the carcinogenic challenge emphasizes the importance of gene x environment interactions. The challenge to rodent geneticists now is to capitalize on the ability to control the genetics and environment in rodent models of tumorigenesis to better understand the biology of breast cancer development, to identify those polymorphisms most relevant to human susceptibility and to identify compensatory pathways that can be targeted for improved prevention in women at highest risk of developing breast cancer.
登录
查看更多内容
影响因子：
64.8
作者：
DONEHOWER, LA;HARVEY, M;BRADLEY, A
通讯作者：
BRADLEY, A
影响因子：
64.5
作者：
Bond, GL;Hu, WW;Levine, AJ
通讯作者：
Levine, AJ
影响因子：
3.7
作者：
Fang, Shenying;Krahe, Ralf;Amos, Christopher I.
通讯作者：
Amos, Christopher I.
影响因子：
7.4
作者：
Hsieh, Szu-Min;Look, Maxime P.;Hunter, Kent W.
通讯作者：
Hunter, Kent W.
影响因子：
9.2
作者：
JACKS, T;REMINGTON, L;WEINBERG, RA
通讯作者：
WEINBERG, RA