Department of Medicine, University of Utah, Salt Lake City, UT 84108, USA.
Genes Chromosomes Cancer. 2013 Jul;52(7):595-609. doi: 10.1002/gcc.22056. Epub 2013 Apr 30.
Telomeres are involved in maintaining genomic stability. Previous studies have linked both telomere length (TL) and telomere-related genes with cancer. We evaluated associations between telomere-related genes, TL, and breast cancer risk in an admixed population of US non-Hispanic white (1,481 cases, 1,586 controls) and U.S. Hispanic and Mexican women (2,111 cases, 2,597 controls) from the Breast Cancer Health Disparities Study. TL was assessed in 1,500 women based on their genetic ancestry. TL-related genes assessed were MEN1, MRE11A, RECQL5, TEP1, TERC, TERF2, TERT, TNKS, and TNKS2. Longer TL was associated with increased breast cancer risk [odds ratio (OR) 1.87, 95% confidence interval (CI) 1.38, 2.55], with the highest risk (OR 3.11, 95% CI 1.74, 5.67 p interaction 0.02) among women with high Indigenous American ancestry. Several TL-related single nucleotide polymorphisms had modest association with breast cancer risk overall, including TEP1 rs93886 (OR 0.82, 95% CI 0.70,0.95); TERF2 rs3785074 (OR 1.13, 95% CI 1.03,1.24); TERT rs4246742 (OR 0.85, 95% CI 0.77,0.93); TERT rs10069690 (OR 1.13, 95% CI 1.03,1.24); TERT rs2242652 (OR 1.51, 95% CI 1.11,2.04); and TNKS rs6990300 (OR 0.89, 95% CI 0.81,0.97). Several differences in association were detected by hormone receptor status of tumors. Most notable were associations with TERT rs2736118 (ORadj 6.18, 95% CI 2.90, 13.19) with estrogen receptor negative/progesterone receptor positive (ER-/PR+) tumors and TERT rs2735940 (ORadj 0.73, 95% CI 0.59, 0.91) with ER-/PR- tumors. These data provide support for an association between TL and TL-related genes and risk of breast cancer. The association may be modified by hormone receptor status and genetic ancestry.
端粒参与维持基因组稳定性。先前的研究将端粒长度 (TL) 和与端粒相关的基因与癌症联系起来。我们在美国非西班牙裔白人（1481 例病例，1586 例对照）和美国西班牙裔和墨西哥裔妇女（2111 例病例，2597 例对照）的混合人群中评估了与端粒相关的基因、TL 和乳腺癌风险之间的关联。基于遗传血统，在 1500 名女性中评估了 TL。评估的 TL 相关基因包括 MEN1、MRE11A、RECQL5、TEP1、TERC、TERF2、TERT、TNKS 和 TNKS2。较长的 TL 与乳腺癌风险增加相关[比值比 (OR) 1.87，95%置信区间 (CI) 1.38,2.55]，在具有高土著美洲血统的女性中风险最高（OR 3.11，95%CI 1.74,5.67 p 交互作用 0.02）。几个 TL 相关的单核苷酸多态性与乳腺癌风险总体上存在适度关联，包括 TEP1 rs93886（OR 0.82，95%CI 0.70,0.95）；TERF2 rs3785074（OR 1.13，95%CI 1.03,1.24）；TERT rs4246742（OR 0.85，95%CI 0.77,0.93）；TERT rs10069690（OR 1.13，95%CI 1.03,1.24）；TERT rs2242652（OR 1.51，95%CI 1.11,2.04）；和 TNKS rs6990300（OR 0.89，95%CI 0.81,0.97）。通过肿瘤的激素受体状态检测到关联的几个差异。最值得注意的是与 TERT rs2736118（ORadj 6.18，95%CI 2.90,13.19）与雌激素受体阴性/孕激素受体阳性（ER-/PR+）肿瘤和 TERT rs2735940（ORadj 0.73，95%CI 0.59,0.91）与 ER-/PR-肿瘤相关的关联。这些数据为 TL 和与端粒相关的基因与乳腺癌风险之间的关联提供了支持。该关联可能受到激素受体状态和遗传血统的修饰。
