Conway Kathleen, Edmiston Sharon N, Tse Chiu-Kit, Bryant Christopher, Kuan Pei Fen, Hair Brionna Y, Parrish Eloise A, May Ryan, Swift-Scanlan Theresa
Department of Epidemiology, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Cancer Epidemiol Biomarkers Prev. 2015 Jun;24(6):921-30. doi: 10.1158/1055-9965.EPI-14-1228. Epub 2015 Mar 25.
African American (AA) women are diagnosed with more advanced breast cancers and have worse survival than white women, but a comprehensive understanding of the basis for this disparity remains unclear. Analysis of DNA methylation, an epigenetic mechanism that can regulate gene expression, could help to explain racial differences in breast tumor clinical biology and outcomes.
DNA methylation was evaluated at 1,287 CpGs in the promoters of cancer-related genes in 517 breast tumors of AA (n = 216) or non-AA (n = 301) cases in the Carolina Breast Cancer Study (CBCS).
Multivariable linear regression analysis of all tumors, controlling for age, menopausal status, stage, intrinsic subtype, and multiple comparisons [false discovery rate (FDR)], identified seven CpG probes that showed significant (adjusted P < 0.05) differential methylation between AAs and non-AAs. Stratified analyses detected an additional four CpG probes differing by race within hormone receptor-negative (HR(-)) tumors. Genes differentially methylated by race included DSC2, KCNK4, GSTM1, AXL, DNAJC15, HBII-52, TUSC3, and TES; the methylation state of several of these genes may be associated with worse survival in AAs. TCGA breast tumor data confirmed the differential methylation by race and negative correlations with expression for most of these genes. Several loci also showed racial differences in methylation in peripheral blood leukocytes (PBL) from CBCS cases, indicating that these variations were not necessarily tumor-specific.
Racial differences in the methylation of cancer-related genes are detectable in both tumors and PBLs from breast cancer cases.
Epigenetic variation could contribute to differences in breast tumor development and outcomes between AAs and non-AAs.
非裔美国（AA）女性被诊断出患有更晚期的乳腺癌，且生存率低于白人女性，但对这种差异的根本原因仍缺乏全面了解。DNA甲基化分析作为一种可调节基因表达的表观遗传机制，可能有助于解释乳腺肿瘤临床生物学和预后的种族差异。
在卡罗来纳乳腺癌研究（CBCS）中，对517例AA（n = 216）或非AA（n = 301）病例的乳腺肿瘤中癌症相关基因启动子区域的1287个CpG位点进行DNA甲基化评估。
对所有肿瘤进行多变量线性回归分析，并对年龄、绝经状态、分期、内在亚型和多重比较[错误发现率（FDR）]进行控制，确定了7个CpG探针，显示AA和非AA之间存在显著（校正P < 0.05）的差异甲基化。分层分析在激素受体阴性（HR(-)）肿瘤中检测到另外4个因种族而异的CpG探针。因种族而异的差异甲基化基因包括DSC2、KCNK4、GSTM1、AXL、DNAJC15、HBII-52、TUSC3和TES；其中一些基因的甲基化状态可能与AA患者较差的生存率相关。TCGA乳腺肿瘤数据证实了种族间的差异甲基化以及这些基因中大多数与表达的负相关。几个位点在CBCS病例的外周血白细胞（PBL）中也显示出甲基化的种族差异，表明这些变异不一定是肿瘤特异性的。
在乳腺癌病例的肿瘤和PBL中均可检测到癌症相关基因甲基化方面的种族差异。
表观遗传变异可能导致AA和非AA之间乳腺肿瘤发展和预后的差异。
