A Multi-Center Epidemiologic Study of Breast Cancer In African American Women

乳腺癌是女性中最常见的癌症，是癌症死亡的第二大原因。目前，在包括田纳西州和南卡罗来纳州在内的美国，非裔美国人的乳腺癌死亡率远远高于白人。人们对乳腺癌的病因知之甚少，也不知道什么因素可以解释为什么非裔美国女性比白人女性更容易被诊断出患有更具侵袭性的疾病。最近的全基因组关联研究(GWAS)为研究乳腺癌的病因提供了机会。在中国和欧洲血统的女性中，大约有20个易感基因座已被确定。最近的报告发现，在高加索和中国女性中，乳腺癌风险持续增加，其中一些基因座的数量不断增加。在这个拟议的项目的三年中，我们预计将通过GWAS确定另外15到20个乳腺癌易感基因，包括我们在亚洲女性中进行的研究。这些基因座与非裔美国女性的相关性仍未得到充分调查，我们最近初步调查的数据显示，在 高加索人和中国人不能在非裔美国人中直接复制。作为癌症外展核心下的一个完整项目，这一拟议项目的目的是调查大约21个GWAS确定的基因座，以发现与非裔美国人妇女相关的遗传风险变异。此外，我们将建立一个结合临床和遗传因素的乳腺癌风险评估模型，以更好地识别高危非裔美国女性，因为现有的唯一针对非裔美国人的乳腺癌风险评估模型不包括遗传标记。

Breast cancer, the most frequently diagnosed cancer among women, is the second leading cause of cancer death. Current breast cancer mortality rates in the United States, including Tennessee and South Carolina are considerably higher among African Americans than among Caucasians. Little is understood about the etiology of breast cancer nor do we know what factors might explain why African American women tend to be diagnosed with more aggressive disease than Caucasian women. Recent genome-wide association studies (GWAS) have opened opportunities to investigate breast cancer etiology. Approximately 20 susceptibility loci have been identified from the GWAS conducted among women of Chinese and European ancestry. Recent reports found breast cancer risk consistently increased among Caucasian and Chinese women with an increasing number of some of these loci. During the three years of this proposed project we anticipate an additional 15 to 20 susceptibility loci for breast cancer will be identified through GWAS, including our study conducted among Asian women. The relevance of these loci to African American women remains under-investigated, and data from our recent pilot investigation have showed that the majority of the initially-reported genetic risk variants identified in Caucasian and Chinese cannot be directly replicated among African Americans. As a full project under the Cancer Outreach Core, the purpose of this proposed project is to investigate approximately 21 GWAS-identified loci to discover genetic risk variants relevant for African American women. In addifion, we will establish a breast cancer risk assessment model that incorporates clinical and genetic factors to better identify high-risk African American women since the only existing breast cancer risk assessment model for African Americans does not include genetic markers.