{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:00:55Z","timestamp":1760058055003,"version":"build-2065373602"},"reference-count":38,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,3,10]],"date-time":"2025-03-10T00:00:00Z","timestamp":1741564800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Academia Sinica","award":["40-05-GMM","AS-GC-110-MD02","236e-1100202","NSTC 111-3114-Y-001-001"],"award-info":[{"award-number":["40-05-GMM","AS-GC-110-MD02","236e-1100202","NSTC 111-3114-Y-001-001"]}]},{"name":"National Development Fund, Executive Yuan","award":["40-05-GMM","AS-GC-110-MD02","236e-1100202","NSTC 111-3114-Y-001-001"],"award-info":[{"award-number":["40-05-GMM","AS-GC-110-MD02","236e-1100202","NSTC 111-3114-Y-001-001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Endometrial cancer is the most common gynecologic malignancy in developed countries, and its incidence is rising globally. Genetic predisposition plays a significant role in modulating risk, particularly in Asian populations. In Taiwan, the burden of endometrial cancer has increased, highlighting the need to gain a better understanding of the genetic loci associated with this disease. This retrospective case\u2013control study included 373 endometrial cancer patients and 3730 controls from the Taiwan Precision Medicine Initiative. Genotype data were obtained using the TWB 2.0 SNP chip. Statistical analyses were conducted using PLINK and SPSS, with logistic regression models assessing the associations between genetic variants and endometrial cancer risk. In this study, we identified two SNPs, rs17601876 in CYP19A1 and rs2900478 in SLCO1B1, that were associated with endometrial cancer. The AG\/GG genotypes of rs17601876 showed a protective effect (OR = 0.743, p = 0.006), while the TA\/AA genotypes of rs2900478 exhibited a nonsignificant trend toward an increased risk. Higher BMI, LDL, triglyceride, total cholesterol, and HbA1c, as well as lower HDL, were strongly associated with greater risk. Our findings demonstrated a protective role of rs17601876 in CYP19A1 and further showed its potential impact on estrogen biosynthesis. Genetic factors involved in endometrial cancer risk are an important issue. Further functional studies are needed to validate the present findings.<\/jats:p>","DOI":"10.3390\/ijms26062461","type":"journal-article","created":{"date-parts":[[2025,3,10]],"date-time":"2025-03-10T06:59:59Z","timestamp":1741589999000},"page":"2461","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genetic Variations in CYP19A1 and SLCO1B1 Genes and Their Association with Endometrial Cancer Risk in the Taiwanese Population: A Case\u2013Control Study"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3828-3723","authenticated-orcid":false,"given":"Yu","family":"Wang","sequence":"first","affiliation":[{"name":"Division of Reproductive Endocrinology and Infertility, Department of Obstetrics, Gynecology and Women\u2019s Health, Taichung Veterans General Hospital, Taichung 40705, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4396-0844","authenticated-orcid":false,"given":"Yu-Ru","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Medical Research, Taichung Veterans General Hospital, Taichung 40705, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tzu-Hung","family":"Hsiao","sequence":"additional","affiliation":[{"name":"Department of Medical Research, Taichung Veterans General Hospital, Taichung 40705, Taiwan"},{"name":"Department of Public Health, Fu Jen Catholic University, New Taipei City 24205, Taiwan"},{"name":"Institute of Genomics and Bioinformatics, National Chung Hsing University, Taichung 40227, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8345-5304","authenticated-orcid":false,"given":"I-Chieh","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Medical Research, Taichung Veterans General Hospital, Taichung 40705, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hsiao-Fan","family":"Kung","sequence":"additional","affiliation":[{"name":"Division of Reproductive Endocrinology and Infertility, Department of Obstetrics, Gynecology and Women\u2019s Health, Taichung Veterans General Hospital, Taichung 40705, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.tjog.2015.09.010","article-title":"Incidence and lifetime risk of uterine corpus cancer in Taiwanese women from 1991 to 2010","volume":"56","author":"Lai","year":"2017","journal-title":"Taiwan J. Obstet. Gynecol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"229","DOI":"10.3322\/caac.21834","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. Clin."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.ygyno.2017.08.011","article-title":"Family history of cancer predicts endometrial cancer risk independently of Lynch Syndrome: Implications for genetic counselling","volume":"147","author":"Johnatty","year":"2017","journal-title":"Gynecol. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2167","DOI":"10.1038\/s41436-019-0536-8","article-title":"The proportion of endometrial cancers associated with Lynch syndrome: A systematic review of the literature and meta-analysis","volume":"21","author":"Ryan","year":"2019","journal-title":"Genet. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1038\/ng.812","article-title":"Genome-wide association study identifies a common variant associated with risk of endometrial cancer","volume":"43","author":"Spurdle","year":"2011","journal-title":"Nat. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3166","DOI":"10.1038\/s41467-018-05427-7","article-title":"Identification of nine new susceptibility loci for endometrial cancer","volume":"9","author":"Glubb","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Wang, X., Glubb, D.M., and O\u2019Mara, T.A. (2022). 10 Years of GWAS discovery in endometrial cancer: Aetiology, function and translation. EBioMedicine, 77.","DOI":"10.1016\/j.ebiom.2022.103895"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"106590","DOI":"10.1016\/j.isci.2023.106590","article-title":"Multi-trait genome-wide association study identifies a novel endometrial cancer risk locus that associates with testosterone levels","volume":"26","author":"Wang","year":"2023","journal-title":"iScience"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1007\/s00404-018-5006-z","article-title":"Management of endometrial, ovarian and cervical cancer in the elderly: Current approach to a challenging condition","volume":"299","author":"Vitale","year":"2019","journal-title":"Arch. Gynecol. Obstet."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.ygyno.2019.01.024","article-title":"Disparities in gynecologic cancer genetics evaluation","volume":"153","author":"Hinchcliff","year":"2019","journal-title":"Gynecol. Oncol."},{"key":"ref_11","unstructured":"National Center for Biotechnology Information (NCBI) [Internet] (2025, February 25). Bethesda (MD): National Library of Medicine (US), National Center for Biotechnology Information: rs1760187, Available online: https:\/\/www.ncbi.nlm.nih.gov\/snp\/rs17601876\/#frequency_tab."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1007\/s10552-014-0448-5","article-title":"Associations between CYP19A1 polymorphisms, Native American ancestry, and breast cancer risk and mortality: The Breast Cancer Health Disparities Study","volume":"25","author":"Boone","year":"2014","journal-title":"Cancer Causes Control"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.mce.2018.10.004","article-title":"Local estrogen metabolism (intracrinology) in endometrial cancer: A systematic review","volume":"489","author":"Cornel","year":"2019","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"5008","DOI":"10.1210\/jc.2019-00757","article-title":"Genetic Association Study of Eight Steroid Hormones and Implications for Sexual Dimorphism of Coronary Artery Disease","volume":"104","author":"Pott","year":"2019","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1158\/1055-9965.EPI-08-0689","article-title":"Two estrogen-related variants in CYP19A1 and endometrial cancer risk: A pooled analysis in the Epidemiology of Endometrial Cancer Consortium","volume":"18","author":"Setiawan","year":"2009","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1097\/FJC.0000000000000793","article-title":"Genetic Variations of CYP19A1 Gene and Stroke Susceptibility: A Case-Control Study in the Chinese Han Population","volume":"75","author":"Cai","year":"2020","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1186\/s12944-020-01366-9","article-title":"Association of CYP19A1 and CYP1A2 genetic polymorphisms with type 2 diabetes mellitus risk in the Chinese Han population","volume":"19","author":"Yang","year":"2020","journal-title":"Lipids Health Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1080\/14737159.2024.2387652","article-title":"CYP19A1 polymorphisms and bladder cancer risk in the Chinese Han population","volume":"24","author":"Liang","year":"2024","journal-title":"Expert Rev. Mol. Diagn."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1007\/s12672-019-0358-9","article-title":"Estrogen Signaling in Endometrial Cancer: A Key Oncogenic Pathway with Several Open Questions","volume":"10","author":"Rodriguez","year":"2019","journal-title":"Horm. Cancer"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1002\/cam4.445","article-title":"An estrogen-induced endometrial hyperplasia mouse model recapitulating human disease progression and genetic aberrations","volume":"4","author":"Yang","year":"2015","journal-title":"Cancer Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1677\/erc.0.0100023","article-title":"Endometrial cancer: Experimental models useful for studies on molecular aspects of endometrial cancer and carcinogenesis","volume":"10","author":"Vollmer","year":"2003","journal-title":"Endocr. Relat. Cancer"},{"key":"ref_22","unstructured":"National Center for Biotechnology Information (NCBI) [Internet] (2025, February 25). Bethesda (MD): National Library of Medicine (US), National Center for Biotechnology Information: rs2900478, Available online: https:\/\/www.ncbi.nlm.nih.gov\/snp\/rs2900478."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Dork, T., Hillemanns, P., Tempfer, C., Breu, J., and Fleisch, M.C. (2020). Genetic Susceptibility to Endometrial Cancer: Risk Factors and Clinical Management. Cancers, 12.","DOI":"10.3390\/cancers12092407"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"5068","DOI":"10.1038\/ncomms6068","article-title":"Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins","volume":"5","author":"Postmus","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1007\/s10549-017-4243-3","article-title":"SLCO1B1 polymorphisms and plasma estrone conjugates in postmenopausal women with ER+ breast cancer: Genome-wide association studies of the estrone pathway","volume":"164","author":"Dudenkov","year":"2017","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"R37","DOI":"10.1186\/bcr2859","article-title":"The association of polymorphisms in hormone metabolism pathway genes, menopausal hormone therapy, and breast cancer risk: A nested case-control study in the California Teachers Study cohort","volume":"13","author":"Lee","year":"2011","journal-title":"Breast Cancer Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.ygyno.2015.10.020","article-title":"Body mass index and mortality in endometrial cancer: A systematic review and meta-analysis","volume":"140","author":"Secord","year":"2016","journal-title":"Gynecol. Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"101447","DOI":"10.1016\/j.gore.2024.101447","article-title":"The association between body mass index and molecular subtypes in endometrial carcinoma","volume":"54","author":"Smith","year":"2024","journal-title":"Gynecol. Oncol. Rep."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1002\/ijc.33206","article-title":"Mendelian randomization analyses suggest a role for cholesterol in the development of endometrial cancer","volume":"148","author":"Kho","year":"2021","journal-title":"Int. J. Cancer"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2938","DOI":"10.1002\/ijc.24285","article-title":"Serum lipids and endometrial cancer risk: Results from the HUNT-II study","volume":"124","author":"Lindemann","year":"2009","journal-title":"Int. J. Cancer"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"6722","DOI":"10.1002\/cam4.5463","article-title":"Serum cholesterol and the risk of developing hormonally driven cancers: A narrative review","volume":"12","author":"Murdock","year":"2023","journal-title":"Cancer Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1016\/j.jfma.2020.05.031","article-title":"Identifying endemic areas and estimating the prevalence of hyperlipidemia in Taiwan\u2019s townships","volume":"120","author":"Tsao","year":"2021","journal-title":"J. Formos. Med. Assoc."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1038\/ng.3562","article-title":"Five endometrial cancer risk loci identified through genome-wide association analysis","volume":"48","author":"Cheng","year":"2016","journal-title":"Nat. Genet."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Li, J., Li, X., Quan, C., Li, X., Wan, C., and Wu, X. (2023). Genomic profile of Chinese patients with endometrial carcinoma. BMC Cancer, 23.","DOI":"10.1186\/s12885-023-11382-4"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1159\/000091834","article-title":"Han Chinese cell and genome bank in Taiwan: Purpose, design and ethical considerations","volume":"61","author":"Pan","year":"2006","journal-title":"Hum. Hered."},{"key":"ref_36","first-page":"5321","article-title":"Population structure of Han Chinese in the modern Taiwanese population based on 10,000 participants in the Taiwan Biobank project","volume":"25","author":"Chen","year":"2016","journal-title":"Hum. Mol. Genet."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"235","DOI":"10.2217\/14622416.9.2.235","article-title":"Taiwan Biobank: A project aiming to aid Taiwan\u2019s transition into a biomedical island","volume":"9","author":"Fan","year":"2008","journal-title":"Pharmacogenomics"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1086\/519795","article-title":"PLINK: A tool set for whole-genome association and population-based linkage analyses","volume":"81","author":"Purcell","year":"2007","journal-title":"Am. J. Hum. Genet."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/6\/2461\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:50:03Z","timestamp":1760028603000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/6\/2461"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,10]]},"references-count":38,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2025,3]]}},"alternative-id":["ijms26062461"],"URL":"https:\/\/doi.org\/10.3390\/ijms26062461","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2025,3,10]]}}}