Replication Study of Breast Cancer Susceptibility Genes in Blacks

描述（由申请人提供）：与所有其他种族/民族相比，非洲裔美国人和非洲人经历了不成比例的侵袭性乳腺癌负担，原因尚不清楚和研究不足。非洲裔妇女乳腺癌遗传流行病学数据的缺乏阻碍了创新性预防措施的发展，以缩小健康差距。由于具有潜在大人群归因风险的常见遗传变异可能以不同于欧洲血统女性的方式在非洲血统女性的乳腺癌发生和进展中发挥作用，我们建议在2200例乳腺癌病例和2300例对照的全基因组关联研究中复制5个新的乳腺癌易感位点（涉及11个基因），所有这些都是非洲血统。这项大型研究的DNA样本和流行病学数据是通过尼日利亚乳腺癌研究（非洲人）、巴巴多斯国家癌症研究（非洲巴巴多斯人）、芝加哥乳腺癌孢子和乳腺癌家庭登记处（非洲裔美国人）收集的。我们将采用复制加精细定位策略，对在原始研究中发现的完全相同的snp进行基因分型，并对这5个基因组区域的标签snp和假定的功能变异进行分型。对于非裔美国人，祖先信息标记也将进行基因分型，以控制人口分层。多重归算程序将用于归算非基因分型的变异。逻辑回归将用于检验关联和计算奇比。此外，我们将研究基因与环境的相互作用，因为在三种非洲血统人群中流行病学风险因素存在明显差异。这项研究将促进对非洲裔妇女乳腺癌遗传风险因素的理解，并将在未来制定新的预防策略方面具有宝贵的价值。

DESCRIPTION (provided by applicant): African Americans and Africans experience a disproportionate burden of aggressive breast cancer in comparison to all other racial/ethnic groups for reasons that remain unknown and understudied. The paucity of data on the genetic epidemiology of breast cancer for women of African ancestry hinders the development of innovative prevention to reduce health disparities. Because common genetic variants with potential large population attributable risk may play a role in breast cancer development and progression for women of African ancestry in a way different from women of European ancestry, we propose to replicate 5 novel breast cancer susceptibility loci (involving 11 genes) previously identified in genome-wide association studies in a well-characterized cohort of about 2200 breast cancer cases and 2300 controls, all of African ancestry. DNA samples and epidemiologic data for this large study have been collected through Nigerian Breast Cancer Study (Africans), Barbados National Cancer Study (African Barbadians), and the Chicago Breast SPORE and the Breast Cancer Family Registry (African Americans). We will employ the replication plus fine-mapping strategy to genotype exactly same SNPs identified in original studies and a panel of tagSNPs and putative functional variants in these 5 genomic regions. For African Americans, ancestry informative markers will also be genotyped to control for population stratification. Multiple imputation procedure will be used to impute variants that are not genotyped. Logistic regressions will be used to test the associations and calculate odd ratios. Furthermore, we will examine gene-environment interaction as there are sharp contrasts in epidemiologic risk factors among the three populations of African ancestry. This study will advance understanding the genetic risk factors for breast cancer in women of African descent and will be invaluable in developing novel prevention strategies in the future.