Department of Preventive Medicine, Keck School of Medicine, and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90089, USA, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA, Center for Human Genetics Research, Vanderbilt University, Nashville, TN 37235, USA, National Cancer Institute, Bethesda, MD 20892, USA, M.Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, 02-781 Warsaw, Poland, Cancer Prevention Institute of California, Fremont, CA 94538, USA, Institute of Population Based Cancer Research, Cancer Registry of Norway, N-0304 Oslo, Norway, Division of Cancer Etiology, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA, Department of Epidemiology, Yale School of Public Health, New Haven CT 06520, USA, Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI 96813, USA, Division of Research, Kaiser Permanente Northern California, Oakland, CA 94611, USA, Section of Biostatistics and Epidemiology, Department of Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Lebanon, NH 03756, USA, Division of Endocrinology, Diabetes and Metabolism, Ohio State University, Columbus, OH 43210, USA, Department of Obstetrics and Gynecology, University of California, Davis, CA 95616, USA, Department of Oncology, Wayne State University School of Medicine and Population Studies and Disparities Research, Karmanos Cancer Institute, Detroit, MI 48202, USA and Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA
Department of Preventive Medicine, Keck School of Medicine, and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90089, USA, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA, Center for Human Genetics Research, Vanderbilt University, Nashville, TN 37235, USA, National Cancer Institute, Bethesda, MD 20892, USA, M.Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, 02-781 Warsaw, Poland, Cancer Prevention Institute of California, Fremont, CA 94538, USA, Institute of Population Based Cancer Research, Cancer Registry of Norway, N-0304 Oslo, Norway, Division of Cancer Etiology, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA, Department of Epidemiology, Yale School of Public Health, New Haven CT 06520, USA, Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI 96813, USA, Division of Research, Kaiser Permanente Northern California, Oakland, CA 94611, USA, Section of Biostatistics and Epidemiology, Department of Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Lebanon, NH 03756, USA, Division of Endocrinology, Diabetes and Metabolism, Ohio State University, Columbus, OH 43210, USA, Department of Obstetrics and Gynecology, University of California, Davis, CA 95616, USA, Department of Oncology, Wayne State University School of Medicine and Population Studies and Disparities Research, Karmanos Cancer Institute, Detroit, MI 48202, USA and Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA.
Carcinogenesis. 2014 Sep;35(9):2068-73. doi: 10.1093/carcin/bgu107. Epub 2014 May 15.
Genome-wide association studies (GWAS) have identified a large number of cancer-associated single nucleotide polymorphisms (SNPs), several of which have been associated with multiple cancer sites suggesting pleiotropic effects and shared biological mechanisms across some cancers. We hypothesized that SNPs associated with other cancers may be additionally associated with endometrial cancer. We examined 213 SNPs previously associated with 14 other cancers for their associations with endometrial cancer in 3758 endometrial cancer cases and 5966 controls of European ancestry from two consortia: Population Architecture Using Genomics and Epidemiology and the Epidemiology of Endometrial Cancer Consortium. Study-specific logistic regression estimates adjusted for age, body mass index and the most significant principal components of genetic ancestry were combined using fixed-effect meta-analysis to evaluate the association between each SNP and endometrial cancer risk. A Bonferroni-corrected P value of 2.35×10(-4) was used to determine statistical significance of the associations. SNP rs7679673, ~6.3kb upstream of TET2 and previously reported to be associated with prostate cancer risk, was associated with endometrial cancer risk in the direction opposite to that for prostate cancer [meta-analysis odds ratio = 0.87 (per copy of the C allele), 95% confidence interval = 0.81, 0.93; P = 7.37×10(-5)] with no evidence of heterogeneity across studies (P heterogeneity = 0.66). This pleiotropic analysis is the first to suggest TET2 as a susceptibility locus for endometrial cancer.
全基因组关联研究（GWAS）已经确定了大量与癌症相关的单核苷酸多态性（SNP），其中一些与多种癌症部位相关，表明存在多效性效应和一些癌症之间的共同生物学机制。我们假设与其他癌症相关的 SNP 可能与子宫内膜癌相关。我们研究了 213 个先前与 14 种其他癌症相关的 SNP，以确定它们与两个联盟（使用基因组学和流行病学进行人群结构研究和子宫内膜癌联盟）中的 3758 例子宫内膜癌病例和 5966 例欧洲血统对照之间的关联。使用固定效应荟萃分析，对每个 SNP 与子宫内膜癌风险之间的关联进行了研究特异性逻辑回归估计，这些估计值针对年龄、体重指数和遗传祖先的最显著主要成分进行了调整。采用 Bonferroni 校正的 P 值为 2.35×10(-4)，以确定关联的统计学意义。SNP rs7679673，位于 TET2 的上游约 6.3kb，先前报道与前列腺癌风险相关，与前列腺癌的方向相反与子宫内膜癌风险相关[荟萃分析比值比=0.87（C 等位基因的每一份），95%置信区间=0.81，0.93；P=7.37×10(-5)]，研究之间没有异质性的证据（P 异质性=0.66）。这项多效性分析是第一个表明 TET2 是子宫内膜癌易感性的基因座。
