{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T21:31:14Z","timestamp":1790803874738,"version":"4.1.0"},"reference-count":27,"publisher":"SAGE Publications","issue":"8","license":[{"start":{"date-parts":[[2017,7,14]],"date-time":"2017-07-14T00:00:00Z","timestamp":1499990400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Genetic Testing and Molecular Biomarkers"],"published-print":{"date-parts":[[2017,8,1]]},"abstract":"\n Background:<\/jats:title>\n \n Reproductive history and obesity are among the well-recognized risk factors in the development of breast cancer, which are partially mediated by the increased exposure of breast tissues to estrogens. However, only a few studies have investigated the link between these risk factors and the pattern of methylation signatures in the breast tissue of healthy women. The role of the estrogen receptor 1 (\n ESR1<\/jats:italic>\n ) gene hypermethylation is reportedly important in the development of breast cancer. Thus, it is speculated that such\n ESR1<\/jats:italic>\n epigenetic changes may be influenced or shaped by obesity and reproductive history-related factors before and during breast carcinogenesis.\n <\/jats:p>\n <\/jats:sec>\n \n Materials and Methods:<\/jats:title>\n \n Breast samples were collected from 120 cancer-free women who had undergone cosmetic mammoplasty. DNA was extracted from the breast tissues and, then, the methylation levels at the promoter and exon 1 regions of the\n ESR1<\/jats:italic>\n gene CpG island were determined by using the methylated DNA immunoprecipitation-quantitative PCR assay.\n <\/jats:p>\n <\/jats:sec>\n \n Results:<\/jats:title>\n \n The methylation level of the\n ESR1<\/jats:italic>\n promoter observed in women with a body mass index (BMI) \u226530\u2009kg\/m\n 2<\/jats:sup>\n (\n p<\/jats:italic>\n \u2009\u2264\u20090.001) was higher than in the subgroups of women of BMI <25\u2009kg\/m\n 2<\/jats:sup>\n (\n p<\/jats:italic>\n \u2009<\u20090.001) and BMI 25-29\u2009kg\/m\n 2<\/jats:sup>\n (\n p<\/jats:italic>\n \u2009<\u20090.001) and was also higher in postmenopausal women compared with that in premenopausal women (\n p<\/jats:italic>\n \u2009=\u20090.046). Pearson correlation coefficient analyses also showed that the high methylation of the\n ESR1<\/jats:italic>\n promoter was correlated with increasing age (\n r<\/jats:italic>\n \u2009=\u2009\u22120.246,\n p<\/jats:italic>\n \u2009=\u20090.007) and BMI (\n r<\/jats:italic>\n \u2009=\u2009\u22120.331,\n p<\/jats:italic>\n \u2009\u2264\u20090.001). Finally, linear multivariate regression revealed a significant association between high methylation rates in the\n ESR1<\/jats:italic>\n gene promoter and increased BMI (\u03b2\u2009=\u2009\u22120.285, 95% CI\u2009=\u2009\u22120.457 to \u22120.113,\n p<\/jats:italic>\n \u2009=\u20090.001). Furthermore, a higher methylation level at the\n ESR1<\/jats:italic>\n gene exon 1 was found in the BMI\u2009\u2265\u200930 kg\/m\n 2<\/jats:sup>\n subgroup compared to the BMI 25-29 kg\/m\n 2<\/jats:sup>\n subgroup (\n p<\/jats:italic>\n \u2009=\u20090.023).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion:<\/jats:title>\n \n These findings provide new hints about the relationship between epigenetic changes within the\n ESR1<\/jats:italic>\n gene CpG island and postmenopausal obesity and aging in cancer-free women. In terms of lifestyle intervention opportunities, this study also highlights the significance and feasibility of such interventions for BMI as a modifiable risk factor.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1089\/gtmb.2017.0028","type":"journal-article","created":{"date-parts":[[2017,7,14]],"date-time":"2017-07-14T16:35:30Z","timestamp":1500050130000},"page":"464-470","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":19,"title":["Epigenetic Changes of the\n ESR1<\/i>\n Gene in Breast Tissue of Healthy Women: A Missing Link with Breast Cancer Risk Factors?"],"prefix":"10.1177","volume":"21","author":[{"given":"Abdolreza","family":"Daraei","sequence":"first","affiliation":[{"name":"Tehran University of Medical Sciences","place":["Iran"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pantea","family":"Izadi","sequence":"additional","affiliation":[{"name":"Tehran University of Medical Sciences","place":["Iran"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghasemali","family":"Khorasani","sequence":"additional","affiliation":[{"name":"Tehran University of Medical Sciences","place":["Iran"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nahid","family":"Nafissi","sequence":"additional","affiliation":[{"name":"Iran University of Medical Sciences","place":["Iran"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad Mehdi","family":"Naghizadeh","sequence":"additional","affiliation":[{"name":"Fasa University of Medical Sciences","place":["Iran"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nasim","family":"Younosi","sequence":"additional","affiliation":[{"name":"Shahid Beheshti University of Medical Sciences","place":["Iran"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alipasha","family":"Meysamie","sequence":"additional","affiliation":[{"name":"Tehran University of Medical Sciences","place":["Iran"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaser","family":"Mansoori","sequence":"additional","affiliation":[{"name":"Fasa University of Medical Sciences","place":["Iran"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milad","family":"Bastami","sequence":"additional","affiliation":[{"name":"Tabriz University of Medical Sciences","place":["Iran"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javad","family":"Tavakkoly-Bazzaz","sequence":"additional","affiliation":[{"name":"Tehran University of Medical Sciences","place":["Iran"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2017,7,14]]},"reference":[{"key":"e_1_3_3_2_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1015714305420"},{"key":"e_1_3_3_3_1","doi-asserted-by":"publisher","DOI":"10.4137\/BCBCR.S39384"},{"key":"e_1_3_3_4_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0079391"},{"key":"e_1_3_3_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1582-4934.2009.00924.x"},{"key":"e_1_3_3_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/bcr3493"},{"key":"e_1_3_3_7_1","first-page":"2279","article-title":"Demethylation of the estrogen receptor gene in estrogen receptor-negative breast cancer cells can reactivate estrogen receptor gene expression","volume":"55","author":"Ferguson AT","year":"1995","unstructured":"Ferguson AT, , Lapidus RG, , Baylin SB, et al. (1995) Demethylation of the estrogen receptor gene in estrogen receptor-negative breast cancer cells can reactivate estrogen receptor gene expression. Cancer Res, 55:2279-2283.","journal-title":"Cancer Res"},{"key":"e_1_3_3_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrfmmm.2010.02.007"},{"key":"e_1_3_3_9_1","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-09-0678"},{"key":"e_1_3_3_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-014-3132-2"},{"key":"e_1_3_3_11_1","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-14-1017"},{"key":"e_1_3_3_12_1","doi-asserted-by":"publisher","DOI":"10.4161\/epi.23790"},{"key":"e_1_3_3_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-014-3650-3"},{"key":"e_1_3_3_14_1","doi-asserted-by":"publisher","DOI":"10.4161\/epi.27015"},{"key":"e_1_3_3_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12349"},{"key":"e_1_3_3_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg3230"},{"key":"e_1_3_3_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13277-015-3567-z"},{"key":"e_1_3_3_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12282-012-0384-8"},{"key":"e_1_3_3_19_1","first-page":"805","article-title":"Methylation of estrogen and progesterone receptor gene 5\u2032CpG islands correlates with lack of estrogen and progesterone receptor gene expression in breast tumors","volume":"2","author":"Lapidus RG","year":"1996","unstructured":"Lapidus RG, , Ferguson AT, , Ottaviano YL, et al. (1996) Methylation of estrogen and progesterone receptor gene 5\u2032CpG islands correlates with lack of estrogen and progesterone receptor gene expression in breast tumors. Clin Cancer Res, 2:805-810.","journal-title":"Clin Cancer Res"},{"key":"e_1_3_3_20_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1018778403001"},{"key":"e_1_3_3_21_1","doi-asserted-by":"publisher","DOI":"10.7314\/APJCP.2014.15.7.3041"},{"key":"e_1_3_3_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/epirev\/mxt010"},{"key":"e_1_3_3_23_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-08-1211"},{"key":"e_1_3_3_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0001-6349.2004.00550.x"},{"key":"e_1_3_3_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-0760(03)00390-X"},{"key":"e_1_3_3_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2012.012"},{"key":"e_1_3_3_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-007-9766-6"},{"key":"e_1_3_3_28_1","doi-asserted-by":"publisher","DOI":"10.3892\/br.2013.187"}],"container-title":["Genetic Testing and Molecular Biomarkers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1089\/gtmb.2017.0028","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/gtmb.2017.0028","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/gtmb.2017.0028","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T07:21:21Z","timestamp":1777447281000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1089\/gtmb.2017.0028"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,7,14]]},"references-count":27,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2017,8,1]]}},"alternative-id":["10.1089\/gtmb.2017.0028"],"URL":"https:\/\/doi.org\/10.1089\/gtmb.2017.0028","relation":{},"ISSN":["1945-0265","1945-0257"],"issn-type":[{"value":"1945-0265","type":"print"},{"value":"1945-0257","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,7,14]]}}}