Taylor Nicholas J, Bensen Jeannette T, Poole Charles, Troester Melissa A, Gammon Marilie D, Luo Jingchun, Millikan Robert C, Olshan Andrew F
Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina.
Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina.
Mol Carcinog. 2015 Dec;54(12):1668-77. doi: 10.1002/mc.22238. Epub 2014 Oct 18.
AURKA is a putative low-penetrance tumor susceptibility gene due to its prominent role in cell cycle regulation and centrosomal function. Germline variation in AURKA was evaluated for association with breast cancer and intrinsic breast cancer subtypes in the Carolina Breast Cancer Study (CBCS), a population-based case-control study of African Americans (AA) and Caucasians (Cau). Tag and candidate single nucleotide polymorphisms (SNPs) on AURKA were genotyped in 1946 cases and 1747 controls. In race-stratified analyses adjusted for age and African ancestry, odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate SNP associations with breast cancer. In a race-combined analysis with similar adjustment, these associations were also examined by intrinsic breast cancer subtype. Using dominant models, most AURKA SNPs demonstrated no association with breast cancer in the race-stratified analyses. Among AA, rs6092309 showed an inverse association with breast cancer (OR = 0.69, 95% CI = 0.53-0.90). In the race-combined analyses, rs6099128 had reduced ORs for luminal A (OR = 0.76, 95% CI = 0.60-0.95) and basal-like breast cancer (OR = 0.54, 95% CI = 0.37-0.80). Rs6092309 showed a similar pattern of association with each subtype. Three SNPs (rs6014711, rs911162, rs1047972) had positive associations with basal-like breast cancer, and ORs reduced or close to 1.00 for other subtypes. Our results suggest inverse associations between some AURKA SNPs and overall breast cancer in AA. We found differential associations by specific subtypes and by race. Replication of these findings in larger AA populations would allow more powerful race-stratified subtype analyses.
AURKA是一个假定的低外显率肿瘤易感基因，因其在细胞周期调控和中心体功能中发挥着重要作用。在卡罗来纳乳腺癌研究（CBCS）中，对AURKA的种系变异与乳腺癌及内在性乳腺癌亚型之间的关联进行了评估，该研究是一项针对非裔美国人（AA）和高加索人（Cau）的基于人群的病例对照研究。对1946例病例和1747例对照进行了AURKA上的标签和候选单核苷酸多态性（SNP）基因分型。在按年龄和非洲血统进行调整的种族分层分析中，计算优势比（OR）和95%置信区间（CI）以评估SNP与乳腺癌的关联。在进行类似调整的种族合并分析中，还按内在性乳腺癌亚型检查了这些关联。使用显性模型，在种族分层分析中，大多数AURKA SNP与乳腺癌无关联。在非裔美国人中，rs6092309与乳腺癌呈负相关（OR = 0.69，95% CI = 0.53 - 0.90）。在种族合并分析中，rs6099128在管腔A型（OR = 0.76，95% CI = 0.60 - 0.95）和基底样乳腺癌（OR = 0.54，95% CI = 0.37 - 0.80）中的OR降低。Rs6092309与每种亚型的关联模式相似。三个SNP（rs6014711、rs911162、rs1047972）与基底样乳腺癌呈正相关，而在其他亚型中OR降低或接近1.00。我们的结果表明，某些AURKA SNP与非裔美国人的总体乳腺癌之间存在负相关。我们发现特定亚型和种族之间存在差异关联。在更大的非裔美国人人群中重复这些发现将有助于进行更有力的种族分层亚型分析。
