Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, USA.
Nat Genet. 2011 Oct 30;43(12):1210-4. doi: 10.1038/ng.985.
Estrogen receptor (ER)-negative breast cancer shows a higher incidence in women of African ancestry compared to women of European ancestry. In search of common risk alleles for ER-negative breast cancer, we combined genome-wide association study (GWAS) data from women of African ancestry (1,004 ER-negative cases and 2,745 controls) and European ancestry (1,718 ER-negative cases and 3,670 controls), with replication testing conducted in an additional 2,292 ER-negative cases and 16,901 controls of European ancestry. We identified a common risk variant for ER-negative breast cancer at the TERT-CLPTM1L locus on chromosome 5p15 (rs10069690: per-allele odds ratio (OR) = 1.18 per allele, P = 1.0 × 10(-10)). The variant was also significantly associated with triple-negative (ER-negative, progesterone receptor (PR)-negative and human epidermal growth factor-2 (HER2)-negative) breast cancer (OR = 1.25, P = 1.1 × 10(-9)), particularly in younger women (<50 years of age) (OR = 1.48, P = 1.9 × 10(-9)). Our results identify a genetic locus associated with estrogen receptor negative breast cancer subtypes in multiple populations.
雌激素受体（ER）阴性乳腺癌在非洲裔女性中的发病率高于欧洲裔女性。为了寻找 ER 阴性乳腺癌的常见风险等位基因，我们结合了非洲裔女性（1004 例 ER 阴性病例和 2745 例对照）和欧洲裔女性（1718 例 ER 阴性病例和 3670 例对照）的全基因组关联研究（GWAS）数据，并在另外 2292 例欧洲裔 ER 阴性病例和 16901 例对照中进行了复制测试。我们在 5p15 染色体上的 TERT-CLPTM1L 基因座上发现了一个与 ER 阴性乳腺癌相关的常见风险变异体（rs10069690：每个等位基因的优势比（OR）为 1.18，P=1.0×10(-10)）。该变异体也与三阴性（ER 阴性、孕激素受体（PR）阴性和人表皮生长因子-2（HER2）阴性）乳腺癌显著相关（OR=1.25，P=1.1×10(-9)），尤其是在年轻女性（<50 岁）中（OR=1.48，P=1.9×10(-9)）。我们的研究结果确定了一个与多种人群的雌激素受体阴性乳腺癌亚型相关的遗传基因座。
