An admixture scan in 1,484 African American women with breast cancer.
An admixture scan in 1,484 African American women with breast cancer.
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DOI：
10.1158/1055-9965.epi-09-0464
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发表时间：
2009-11-01
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通讯作者：
Freedman, Matthew L
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作者：
Fejerman, Laura;Haiman, Christopher A;Freedman, Matthew L
与欧洲裔美国女性相比，患有乳腺癌的非裔美国女性更容易患上不表达雌激素受体(ER)和孕激素受体(PR)的侵袭性肿瘤。这种差异是否是遗传因素造成的，目前还没有确定。我们进行了一项基于混合物的全基因组扫描，以寻找乳腺癌的风险等位基因，这些等位基因在非裔美国人和欧洲裔美国女性中的频率高度分化，可能与特定的乳腺癌表型有关，如ER阴性(ER-)疾病。患有浸润性乳腺癌的非裔美国女性(n=1,484)是从6项基于人群的研究中收集的，并在大约1,500个血统信息标记上进行了分型。我们调查了全球遗传祖先，并进行了全基因组混合扫描，寻找与疾病表型相关的乳腺癌易感基因。在控制了可能的混杂因素后，我们发现ER+PR+和ER-PR-女性的血统有显著差异，ER+PR+个体的欧洲血统较高(欧洲血统比例0：1变化的优势比为2.84；95%可信区间为1.13-7.14；P=0.026)。有局部肿瘤的女性的欧洲血统高于非局部肿瘤的女性(优势比为2.65；95%可信区间为1.11~6.35；P=0.029)。在全基因组范围内，没有观察到任何特定基因的欧洲或非洲血统与乳腺癌之间的显著相关性，或者在按ER/PR状态、分期或级别分层的分析中没有观察到。总之，在非裔美国女性中，基因血统与ER/PR状态和疾病分期有关。然而，我们发现几乎没有证据表明任何一个地区的遗传祖先对乳腺癌风险或激素受体状态有显著影响。
African American women with breast cancer present more commonly with aggressive tumors that do not express the estrogen receptor (ER) and progesterone receptor (PR) compared with European American women. Whether this disparity is the result of inherited factors has not been established. We did an admixture-based genome-wide scan to search for risk alleles for breast cancer that are highly differentiated in frequency between African American and European American women, and may contribute to specific breast cancer phenotypes, such as ER-negative (ER-) disease. African American women with invasive breast cancer (n = 1,484) were pooled from six population-based studies and typed at approximately 1,500 ancestry-informative markers. We investigated global genetic ancestry and did a whole genome admixture scan searching for breast cancer-predisposing loci in association with disease phenotypes. We found a significant difference in ancestry between ER+PR+ and ER-PR- women, with higher European ancestry among ER+PR+ individuals, after controlling for possible confounders (odds ratios for a 0 to 1 change in European ancestry proportion, 2.84; 95% confidence interval, 1.13-7.14; P = 0.026). Women with localized tumors had higher European ancestry than women with non-localized tumors (odds ratios, 2.65; 95% confidence interval, 1.11-6.35; P = 0.029). No genome-wide statistically significant associations were observed between European or African ancestry at any specific locus and breast cancer, or in analyses stratified by ER/PR status, stage, or grade. In summary, in African American women, genetic ancestry is associated with ER/PR status and disease stage. However, we found little evidence that genetic ancestry at any one region contributes significantly to breast cancer risk or hormone receptor status.