Objective: 

To investigate the impact of global and local genetic ancestry and neighborhood socioeconomic status (nSES), on breast cancer (BC) subtype, and gene expression.

Background: 

Higher rates of aggressive BC subtypes [triple negative breast cancer (TNBC)] and worse overall BC survival are seen in black women [Hispanic Black (HB) and non-Hispanic Black (NHB)] and women from low nSES. However, the complex relationship between genetic ancestry, nSES, and BC subtype etiology remains unknown.

Methods: 

Genomic analysis was performed on the peripheral blood from a cohort of 308 stage I to IV non-Hispanic White (NHW), Hispanic White (HW), HB, and NHB women with BC. Patient and tumor characteristics were collected. Global and local ancestral estimates were calculated. Multinomial logistic regression was performed to determine associations between age, stage, genetic ancestry, and nSES on rates of TNBC compared to estrogen receptor (ER+)/epidermal growth factor receptor 2 (HER2−), ER+/HER2+, and ER−/HER2+ disease.

Results: 

Among 308 women, we identified a significant association between increasing West African (WA) ancestry and odds of TNBC [odds ratio (OR): 1.06, 95% confidence interval (95% CI): 1.001–1.126, P=0.046] as well as an inverse relationship between higher nSES and TNBC (OR: 0.343, 95% CI: 0.151–0.781, P=0.011). WA ancestry remained significantly associated with TNBC when adjusting for patient age and tumor stage, but not when adjusting for nSES (OR: 1.049, 95% CI: −0.987–1.116, P=0.120). Local ancestry analysis, however, still revealed nSES-independent enriched WA ancestral segment centered at χ²=42004914 (p=3.70×10⁻⁵) in patients with TNBC.

Conclusions: 

In this translational epidemiologic study of genetic ancestry and nSES on BC subtype, we discovered associations between increasing WA ancestry, low nSES, and higher rates of TNBC compared to other BC subtypes. Moreover, on admixture mapping, specific chromosomal segments were associated with WA ancestry and TNBC, independent of nSES. However, on multinomial logistic regression adjusting for WA ancestry, women from low nSES were more likely to have TNBC, independent of genetic ancestry. These findings highlight the complex nature of TNBC and the importance of studying potential gene-environment interactions as drivers of TNBC.

中文翻译：

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转化流行病学：确定三阴性乳腺癌遗传祖先与社区社会经济状况之间相互作用的综合方法

客观的： 

调查全球和本地遗传血统和邻里社会经济地位 (nSES) 对乳腺癌 (BC) 亚型和基因表达的影响。

背景： 

在黑人女性 [西班牙裔黑人 (HB) 和非西班牙裔黑人 (NHB)] 和来自低 nSES 的女性中，侵袭性 BC 亚型 [三阴性乳腺癌 (TNBC)] 的发生率更高，整体 BC 生存率更差。然而，遗传血统、nSES 和 BC 亚型病因之间的复杂关系仍然未知。

方法： 

对 308 名 I 至 IV 期非西班牙裔白人 (NHW)、西班牙裔白人 (HW)、HB 和 NHB 患有 BC 的女性的外周血进行基因组分析。收集患者和肿瘤特征。计算了全球和当地的祖先估计。进行多项逻辑回归以确定与雌激素受体 (ER+)/表皮生长因子受体 2 (HER2-)、ER+/HER2+ 和 ER-/HER2+ 疾病相比，年龄、阶段、遗传血统和 nSES 与 TNBC 发病率之间的关联.

结果： 

在 308 名女性中，我们发现增加的西非 (WA) 血统与 TNBC 的几率之间存在显着关联 [优势比 (OR): 1.06, 95% 置信区间 (95% CI): 1.001–1.126, P = 0.046]作为较高 nSES 和 TNBC 之间的反比关系（OR：0.343，95% CI：0.151–0.781，P = 0.011）。在调整患者年龄和肿瘤分期时，西澳血统仍与 TNBC 显着相关，但在调整 nSES 时则没有（OR：1.049，95% CI：-0.987-1.116，P = 0.120）。然而，本地血统分析仍然显示 TNBC 患者中不依赖于 nSES 的富集 WA 祖先节段以 χ ² =42004914 ( p =3.70×10 ^-5 ) 为中心。

结论： 

在这项关于 BC 亚型的遗传血统和 nSES 的转化流行病学研究中，我们发现与其他 BC 亚型相比，增加 WA 血统、低 nSES 和更高的 TNBC 发生率之间存在关联。此外，在混合图谱中，特定的染色体片段与 WA 血统和 TNBC 相关，与 nSES 无关。然而，在针对 WA 血统进行多项逻辑回归调整时，来自低 nSES 的女性更有可能患有 TNBC，与遗传血统无关。这些发现强调了 TNBC 的复杂性以及研究潜在基因-环境相互作用作为 TNBC 驱动因素的重要性。