Women of Latin American origin in the United States are more likely to be diagnosed with advanced breast cancer and have a higher risk of mortality than non-Hispanic White women. Studies in U.S. Latinas and Latin American women have reported a high incidence of HER2 positive (+) tumors; however, the factors contributing to this observation are unknown. Genome-wide genotype data for 1,312 patients from the Peruvian Genetics and Genomics of Breast Cancer Study (PEGEN-BC) were used to estimate genetic ancestry. We tested the association between HER2 status and genetic ancestry using logistic and multinomial logistic regression models. Findings were replicated in 616 samples from Mexico and Colombia. Average Indigenous American (IA) ancestry differed by subtype. In multivariate models, the odds of having an HER2+ tumor increased by a factor of 1.20 with every 10% increase in IA ancestry proportion (95% CI, 1.07-1.35; P = 0.001). The association between HER2 status and IA ancestry was independently replicated in samples from Mexico and Colombia. Results suggest that the high prevalence of HER2+ tumors in Latinas could be due in part to the presence of population-specific genetic variant(s) affecting HER2 expression in breast cancer. SIGNIFICANCE: The positive association between Indigenous American genetic ancestry and HER2+ breast cancer suggests that the high incidence of HER2+ subtypes in Latinas might be due to population and subtype-specific genetic risk variants.

中文翻译：

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人类表皮生长因子受体 2 阳性乳腺癌与拉丁美洲女性的美国原住民血统有关。


在美国，拉丁美洲裔女性比非西班牙裔白人女性更有可能被诊断出患有晚期乳腺癌，并且死亡风险更高。对美国拉丁裔和拉丁美洲女性的研究表明 HER2 阳性 (+) 肿瘤的发病率很高；然而，促成这一观察结果的因素尚不清楚。来自秘鲁乳腺癌遗传学和基因组学研究 (PEGEN-BC) 的 1,312 名患者的全基因组基因型数据用于估计遗传血统。我们使用逻辑回归模型和多项逻辑回归模型测试了 HER2 状态与遗传血统之间的关联。研究结果在墨西哥和哥伦比亚的 616 个样本中得到了重复。美洲原住民 (IA) 的平均血统因亚型而异。在多变量模型中，IA 血统比例每增加 10%，患 HER2+ 肿瘤的几率就会增加 1.20 倍（95% CI，1.07-1.35；P = 0.001）。 HER2 状态与 IA 血统之间的关联在墨西哥和哥伦比亚的样本中独立复制。结果表明，拉丁美洲人 HER2+ 肿瘤的高患病率可能部分归因于影响乳腺癌中 HER2 表达的人群特异性遗传变异的存在。意义：美国原住民遗传血统与 HER2+ 乳腺癌之间的正相关表明，拉丁美洲人 HER2+ 亚型的高发病率可能是由于人群和亚型特异性遗传风险变异所致。