Cell Cycle/Apoptosis Gene Variants and Breast Cancer Risk

细胞周期/凋亡基因变异和乳腺癌风险

• 批准号: 8075439
• 负责人: QIUYIN CAI
• 金额: $ 51.52万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-15 至 2013-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8075439
• 关键词: Accounting; Address; Adult; Animals; Apoptosis; Biological; Breast; Breast Cancer Prevention; Cancer-Predisposing Gene; Candidate Disease Gene; Cell Cycle; Cell Cycle Regulation; Cell Proliferation; Cells; Cessation of life; Communities; Control Groups; Data; Data Collection; Disease Association; Epidemiologic Studies; Equilibrium; Estrogen Metabolism; Estrogens; Etiology; Evaluation; General Population; Genes; Genetic; Genetic Polymorphism; Genetic Variation; Genomics; Genotype; Haplotypes; High Risk Woman; In Vitro; Knowledge; Maintenance; Malignant Neoplasms; Methodology; Minority; Molecular; Mutate; Neoplasms; Pathway interactions; Penetrance; Phase; Play; Population Study; Primary Prevention; Recruitment Activity; Research Design; Risk; Role; Sampling; Secondary Prevention; Specimen; Statistical Methods; Variant; base; breast tumorigenesis; cancer cell; cancer risk; cancer therapy; carcinogenesis; case control; cell injury; gene environment interaction; gene interaction; genetic variant; human tissue; insight; malignant breast neoplasm; phase 1 study; phase 2 study; research study; response

DESCRIPTION (provided by applicant): It is well established that genetic factors play a major role in breast tumorigenesis. However, the known breast cancer susceptibility genes account for only a minority of breast cancer cases in the general population. Cumulative evidence from in vitro and animal studies suggests that the genes involved in the cell-cycle control and apoptosis pathways may be related to breast cancer. The cell-cycle control and apoptosis pathways function as an integrated molecular network, and perturbations in one pathway can have profound consequences on the other. In this application, we propose to investigate genetic variations of major genes involved in the cell- cycle control and apoptosis pathways in relation to breast cancer risk. The proposed study will use data and biological samples collected from the Shanghai Breast Cancer Study (SBCS, R01CA64277). Genetic polymorphisms in 25 candidate genes in the cell-cycle control and apoptosis pathways will initially be evaluated using both the genotype- and haplotype- approaches in 1,250 cases and 1,250 controls recruited from 1996 to 1998. Promising associations identified in the initial phase will be re-evaluated in a second set of subjects (1,850 cases and 1,850 controls) recruited from 2002 to 2005. This two-phase study design will effectively balance both Type I and Type 2 statistical errors and provide credible results towards our understanding of the etiology of breast cancer. We will use the multifactor-dimensionality reduction (MDR) statistical method to investigate any gene-gene interaction in relation to breast cancer risk. We will investigate interaction between genetic polymorphisms with endogenous estrogen exposure related factors in relation to breast cancer risk. We will evaluate whether genetic polymorphisms may be associated with the risk of specific subtypes of breast cancer. We will also conduct in vitro experiments to evaluate the function of genetic variations to further confirm the biological relevance of the association. With its large size and strong methodology, the SBCS provides a great opportunity to investigate gene-gene and gene-environment interactions in relation to breast cancer risk. The findings from the proposed study are likely to significantly advance our knowledge of the etiology of breast cancer and will be valuable for identifying high risk women for the primary and secondary prevention of breast cancer. We propose to investigate genetic variations of major genes involved in the cell-cycle control and apoptosis pathways in relation to breast cancer risk. The findings from the proposed study are likely to significantly advance our knowledge of the etiology of breast cancer and will be valuable for identifying high risk women for the primary and secondary prevention of breast cancer.

描述（由申请人提供）：遗传因素在乳腺肿瘤发生中起主要作用已被证实。然而，已知的乳腺癌易感基因只占普通人群中乳腺癌病例的一小部分。体外和动物实验的累积证据表明，参与细胞周期控制和细胞凋亡途径的基因可能与乳腺癌有关。细胞周期控制和凋亡通路作为一个完整的分子网络起作用，其中一条通路的扰动可以对另一条通路产生深远的影响。在这个应用中，我们建议研究与乳腺癌风险相关的细胞周期控制和细胞凋亡途径的主要基因的遗传变异。拟议的研究将使用从上海乳腺癌研究（SBCS, R01CA64277）收集的数据和生物样本。在细胞周期控制和细胞凋亡途径中，25个候选基因的遗传多态性将首先使用基因型和单倍型方法对1996年至1998年招募的1250例病例和1250例对照进行评估。将在2002年至2005年招募的第二组受试者（1850例病例和1850例对照）中重新评估在初始阶段确定的有希望的关联。这个两阶段的研究设计将有效地平衡I型和2型统计误差，并为我们对乳腺癌病因的理解提供可信的结果。我们将使用多因素降维（MDR）统计方法来调查任何与乳腺癌风险相关的基因-基因相互作用。我们将研究遗传多态性与内源性雌激素暴露相关因素与乳腺癌风险之间的相互作用。我们将评估遗传多态性是否可能与乳腺癌特定亚型的风险相关。我们还将进行体外实验来评估遗传变异的功能，以进一步确认这种关联的生物学相关性。凭借其庞大的规模和强大的方法，SBCS为研究与乳腺癌风险相关的基因-基因和基因-环境相互作用提供了一个很好的机会。这项研究的结果可能会大大提高我们对乳腺癌病因的认识，并对确定高危妇女进行乳腺癌的一级和二级预防有价值。

项目成果

The matrix metalloproteinase-7 polymorphism rs10895304 is associated with increased recurrence risk in patients with clinically localized prostate cancer.

基质金属蛋白酶 7 多态性 rs10895304 与临床局限性前列腺癌患者复发风险增加相关。

• DOI: 10.1016/j.ijrobp.2010.01.013
• 发表时间: 2011
• 期刊: International journal of radiation oncology, biology, physics
• 作者: Jaboin,JerryJ;Hwang,Misun;Lopater,Zachary;Chen,Heidi;Ray,GeoffreyL;Perez,Carmen;Cai,Qiuyin;Wills,MarciaL;Lu,Bo
• 通讯作者: Lu,Bo