{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T23:45:57Z","timestamp":1790120757357,"version":"4.0.1"},"reference-count":120,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2010,12,31]],"date-time":"2010-12-31T00:00:00Z","timestamp":1293753600000},"content-version":"vor","delay-in-days":790,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Obstet Gynecol Scand"],"published-print":{"date-parts":[[2008,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>Objective.<\/jats:italic> Endometrial cancer is one of the most common invasive gynecologic malignancies in developed countries and the eighth leading cause of cancer death in women; it typically arises in the sixth or seventh decade of life. The aim of this review was to evaluate possible roles of genetic and socio\u2010biological factors in type I endometrial cancer, largely confined to pre\u2010 and perimenopausal women, with a history of estrogen exposure and\/or endometrial hyperplasia. <jats:italic>Methods<\/jats:italic>. An extensive literature review, from 1990 to 2007 was performed on modifiable risk factors for type I endometrial cancer. Additionally, carcinogenesis mechanisms, biomarker and hormonal and biomolecular approaches to cancer detection, progression and monitoring and socio\u2010biological factors were reviewed. <jats:italic>Results.<\/jats:italic> Several socio\u2010biological and lifestyle characteristics, such as hormone replacement therapy, glycemic index, obesity, alcohol use, antipsychotic medication, melatonin, physical activity and variants in hormone metabolism genes have been identified as risk factors for developing endometrial cancer of type I, the majority of which are associated with excess estrogens causing continued stimulation of the endometrium. There is a genetic link to non\u2010polyposis colorectal cancer syndrome, but association of endometrial cancer risk to other genetic polymorphisms has yielded conflicting results. <jats:italic>Conclusions<\/jats:italic>. Many factors linked to hormonal imbalance, such as obesity, weight change, body size, alcohol, hyper\u2010androgenic states, glycemic index and antidepressant agents, influence the endometrial cancer risk, central to which are endogenous and exogenous estrogen hyperstimulation of the endometrium. Conversely, smoking cigarettes, diet, physical activity and melatonin production seem to reduce the risk of cancer development. Other external factors fit well with the unopposed estrogen theory, but more studies are needed to investigate modifiable and added risk factors for endometrial cancer.<\/jats:p>","DOI":"10.1080\/00016340802160079","type":"journal-article","created":{"date-parts":[[2008,6,20]],"date-time":"2008-06-20T14:01:56Z","timestamp":1213970516000},"page":"1101-1113","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Hormonal carcinogenesis and socio\u2010biological development factors in endometrial cancer: A clinical review"],"prefix":"10.1111","volume":"87","author":[{"given":"ANDREA","family":"TINELLI","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"DANIELE","family":"VERGARA","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ROBERTA","family":"MARTIGNAGO","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"GIUSEPPE","family":"LEO","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ANTONIO","family":"MALVASI","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"RAFFAELE","family":"TINELLI","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2010,12,31]]},"reference":[{"key":"e_1_2_5_2_2","doi-asserted-by":"publisher","DOI":"10.3322\/canjclin.49.1.8"},{"key":"e_1_2_5_3_2","doi-asserted-by":"crossref","first-page":"74","DOI":"10.3322\/canjclin.55.2.74","article-title":"Global cancer statistics","volume":"55","author":"Max Parkin D","year":"2005","journal-title":"Cancer J Clin"},{"key":"e_1_2_5_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1879"},{"key":"e_1_2_5_5_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pathol.2.010506.091905"},{"key":"e_1_2_5_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature04225"},{"key":"e_1_2_5_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/0029-7844(94)00383-O"},{"key":"e_1_2_5_8_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.288.3.321"},{"key":"e_1_2_5_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)66455-0"},{"key":"e_1_2_5_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwj316"},{"key":"e_1_2_5_11_2","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-03-0241"},{"issue":"1","key":"e_1_2_5_12_2","first-page":"848","article-title":"Risk of endometrial cancer and estrogen replacement therapy history by cyp17 genotype","volume":"61","author":"McKean\u2010Cowdin R","year":"2001","journal-title":"Cancer Res"},{"key":"e_1_2_5_13_2","first-page":"3955","article-title":"A Polymorphism in CYP17 and endometrial cancer risk","volume":"61","author":"Haiman CA","year":"2001","journal-title":"Cancer Res"},{"key":"e_1_2_5_14_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1525-1438.2006.00417.x"},{"key":"e_1_2_5_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2004.01.001"},{"key":"e_1_2_5_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.21041"},{"issue":"3","key":"e_1_2_5_17_2","first-page":"411","article-title":"The T\/C polymorphism of the CYP17 gene and G\/A polymorphism of the CYP19 gene in endometrial cancer","volume":"25","author":"Szyllo K","year":"2006","journal-title":"J Exp Clin Cancer Res"},{"key":"e_1_2_5_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-4731(86)90080-4"},{"key":"e_1_2_5_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-2744(199607)16:3<149::AID-MC5>3.0.CO;2-C"},{"key":"e_1_2_5_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/368237a0"},{"key":"e_1_2_5_21_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-03-3295"},{"key":"e_1_2_5_22_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-2857"},{"issue":"63","key":"e_1_2_5_23_2","first-page":"3913","article-title":"CYP1B1 Gene polymorphisms have higher risk for endometrial cancer, and positive correlations with estrogen receptor \u03b1 and estrogen receptor \u03b2 expressions","volume":"15","author":"Sasaki M","year":"2003","journal-title":"Cancer Res"},{"key":"e_1_2_5_24_2","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgh039"},{"key":"e_1_2_5_25_2","doi-asserted-by":"publisher","DOI":"10.1124\/mol.104.006056"},{"key":"e_1_2_5_26_2","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1158\/1055-9965.1515.13.9","article-title":"Cytochrome P450 1B1 gene polymorphisms and postmenopausal endometrial cancer risk","volume":"13","author":"Rylander\u2010Rudqvist T","year":"2004","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"e_1_2_5_27_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1990.tb08280.x"},{"key":"e_1_2_5_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2004.09.057"},{"key":"e_1_2_5_29_2","first-page":"881","article-title":"Progesterone inhibits human endometrial cancer cell growth and invasiveness: down\u2010regulation of cellular adhesion molecules through progesterone B receptors","volume":"62","author":"Dai D","year":"2002","journal-title":"Cancer Res"},{"key":"e_1_2_5_30_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349-7006.2006.00332.x"},{"key":"e_1_2_5_31_2","first-page":"4576","article-title":"Relative expression of progesterone receptors A and B in endometrioid cancers of the endometrium","volume":"61","author":"Arnett\u2010Mansfield RL","year":"2001","journal-title":"Cancer Res"},{"key":"e_1_2_5_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2004.07.007"},{"key":"e_1_2_5_33_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.192172299"},{"key":"e_1_2_5_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.1995.92"},{"key":"e_1_2_5_35_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2004-0114"},{"key":"e_1_2_5_36_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.1738"},{"key":"e_1_2_5_37_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1525-1438.2006.00767.x"},{"key":"e_1_2_5_38_2","first-page":"97","article-title":"Progesterone receptor B gene inactivation and CpG hypermethylation in human uterine endometrial cancer","volume":"61","author":"Sasaki M","year":"2001","journal-title":"Cancer Res"},{"key":"e_1_2_5_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2005.05.035"},{"key":"e_1_2_5_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cancergencyto.2007.02.002"},{"key":"e_1_2_5_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd1930"},{"key":"e_1_2_5_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2005.09.044"},{"key":"e_1_2_5_43_2","first-page":"1531","article-title":"Obesity, endogenous hormones, and endometrial cancer risk: a synthetic review","volume":"11","author":"Kaaks R","year":"2002","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"e_1_2_5_44_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/22.15.3181"},{"key":"e_1_2_5_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2005.01.104"},{"key":"e_1_2_5_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(03)00883-0"},{"key":"e_1_2_5_47_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.21516"},{"key":"e_1_2_5_48_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.21436"},{"key":"e_1_2_5_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cancergencyto.2006.10.001"},{"key":"e_1_2_5_50_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0215(200002)9999:9999<::AID-IJC1053>3.0.CO;2-T"},{"key":"e_1_2_5_51_2","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/45.1.277"},{"key":"e_1_2_5_52_2","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-46-1-146"},{"key":"e_1_2_5_53_2","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyi226"},{"key":"e_1_2_5_54_2","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyi223"},{"issue":"22","key":"e_1_2_5_55_2","first-page":"5077","article-title":"Diet, body size, physical activity, and the risk of endometrial cancer","volume":"57","author":"Goodman MT","year":"1997","journal-title":"Cancer Res"},{"key":"e_1_2_5_56_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.aje.a009270"},{"key":"e_1_2_5_57_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-006-9405-7"},{"key":"e_1_2_5_58_2","doi-asserted-by":"publisher","DOI":"10.1207\/S15327914NC441_3"},{"key":"e_1_2_5_59_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6602609"},{"key":"e_1_2_5_60_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6603458"},{"key":"e_1_2_5_61_2","doi-asserted-by":"publisher","DOI":"10.1159\/000063081"},{"key":"e_1_2_5_62_2","doi-asserted-by":"publisher","DOI":"10.1159\/000066230"},{"key":"e_1_2_5_63_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.81.3.935"},{"key":"e_1_2_5_64_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo-113-1-297"},{"key":"e_1_2_5_65_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.76.5.1115"},{"key":"e_1_2_5_66_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.75.5.1235"},{"key":"e_1_2_5_67_2","first-page":"3019","article-title":"Insulin\u2010like growth factor I receptors in normal and neoplastic human endometrium","volume":"50","author":"Talavera F","year":"1990","journal-title":"Cancer Res"},{"issue":"5","key":"e_1_2_5_68_2","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1158\/1055-9965.748.13.5","article-title":"Increased plasma levels of insulin like growth factor 2 and insulin\u2010like growth factor binding protein 3 are associated with endometrial cancer risk","volume":"13","author":"Oh JC","year":"2004","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"e_1_2_5_69_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.11544"},{"key":"e_1_2_5_70_2","doi-asserted-by":"publisher","DOI":"10.1207\/S15327914NC4501_3"},{"key":"e_1_2_5_71_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1011201911664"},{"key":"e_1_2_5_72_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10552-007-0127-x"},{"key":"e_1_2_5_73_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.1334"},{"key":"e_1_2_5_74_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejcn.1602519"},{"key":"e_1_2_5_75_2","doi-asserted-by":"publisher","DOI":"10.1159\/000067769"},{"key":"e_1_2_5_76_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1011201911664"},{"key":"e_1_2_5_77_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.20821"},{"key":"e_1_2_5_78_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.22990"},{"key":"e_1_2_5_79_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2001.tb02740.x"},{"key":"e_1_2_5_80_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.10974"},{"key":"e_1_2_5_81_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djh291"},{"key":"e_1_2_5_82_2","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/154.10.924"},{"key":"e_1_2_5_83_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1047-2797(96)00071-3"},{"key":"e_1_2_5_84_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0215(19990702)82:1<38::AID-IJC8>3.0.CO;2-Q"},{"key":"e_1_2_5_85_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1008919717930"},{"key":"e_1_2_5_86_2","first-page":"1531","article-title":"Obesity, endogenous hormones, and endometrial cancer risk: a synthetic review","volume":"11","author":"Kaaks R","year":"2002","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"e_1_2_5_87_2","first-page":"287","article-title":"Physical activity and cancer prevention: from observational to intervention research","volume":"10","author":"Friedenreich CM","year":"2001","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"e_1_2_5_88_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpobgyn.2005.10.010"},{"key":"e_1_2_5_89_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1106561"},{"key":"e_1_2_5_90_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000205848.83210.73"},{"key":"e_1_2_5_91_2","doi-asserted-by":"publisher","DOI":"10.1079\/PNS200070"},{"key":"e_1_2_5_92_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.279.9.669"},{"key":"e_1_2_5_93_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-2000-8847"},{"key":"e_1_2_5_94_2","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.23.4.449"},{"key":"e_1_2_5_95_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1022518321634"},{"key":"e_1_2_5_96_2","doi-asserted-by":"publisher","DOI":"10.1038\/oby.2003.145"},{"key":"e_1_2_5_97_2","doi-asserted-by":"publisher","DOI":"10.1210\/er.18.6.801"},{"key":"e_1_2_5_98_2","doi-asserted-by":"publisher","DOI":"10.1038\/oby.2002.140"},{"key":"e_1_2_5_99_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-03-3393"},{"key":"e_1_2_5_100_2","doi-asserted-by":"publisher","DOI":"10.1079\/PNS200068"},{"key":"e_1_2_5_101_2","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-05-0493"},{"key":"e_1_2_5_102_2","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1158\/1055-9965.868.13.5","article-title":"Effects of a moderate intensity exercise intervention on estrogen metabolism in postmenopausal women","volume":"13","author":"Atkinson C","year":"2004","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"e_1_2_5_103_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2004.12.011"},{"key":"e_1_2_5_104_2","doi-asserted-by":"publisher","DOI":"10.2165\/00007256-200131020-00004"},{"key":"e_1_2_5_105_2","doi-asserted-by":"publisher","DOI":"10.1139\/y98-055"},{"key":"e_1_2_5_106_2","doi-asserted-by":"publisher","DOI":"10.2165\/00007256-199826050-00002"},{"key":"e_1_2_5_107_2","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1139\/y98-050","article-title":"Cellular responses to moderate and heavy exercise","volume":"76","author":"Nehlsen\u2010Cannarella SL","year":"1998","journal-title":"Can J Physiol Pharmacol"},{"key":"e_1_2_5_108_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1047-2797(96)00071-3"},{"key":"e_1_2_5_109_2","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/154.10.924"},{"key":"e_1_2_5_110_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1024866827775"},{"key":"e_1_2_5_111_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0215(19990702)82:1<38::AID-IJC8>3.0.CO;2-Q"},{"key":"e_1_2_5_112_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djh291"},{"key":"e_1_2_5_113_2","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-04-0665"},{"issue":"1","key":"e_1_2_5_114_2","first-page":"89","article-title":"Is the pineal gland involved in the pathogenesis of endometrial carcinoma","volume":"62","author":"Sandyk R","year":"1992","journal-title":"Int J Neurosci"},{"issue":"2","key":"e_1_2_5_115_2","first-page":"109","article-title":"Serum melatonin circadian profile in women suffering from the genital tract cancers","volume":"21","author":"Karasek M","year":"2000","journal-title":"Neuro Endocrinol Lett"},{"key":"e_1_2_5_116_2","doi-asserted-by":"publisher","DOI":"10.1159\/000009926"},{"key":"e_1_2_5_117_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-079X.2000.280405.x"},{"issue":"2","key":"e_1_2_5_118_2","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1046\/j.1439-0434.2002.00691_2.x-i1","article-title":"Melatonin binding sites in estrogen receptor\u2010positive cells derived from human endometrial cancer","volume":"35","author":"Kobayashi Y","year":"2003","journal-title":"J Pineal Res"},{"key":"e_1_2_5_119_2","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-06-0257"},{"key":"e_1_2_5_120_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1525-1438.2006.00572.x"},{"key":"e_1_2_5_121_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-1114"}],"container-title":["Acta Obstetricia et Gynecologica Scandinavica"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1080%2F00016340802160079","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/obgyn.onlinelibrary.wiley.com\/doi\/pdf\/10.1080\/00016340802160079","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T00:24:05Z","timestamp":1696983845000},"score":1,"resource":{"primary":{"URL":"https:\/\/obgyn.onlinelibrary.wiley.com\/doi\/10.1080\/00016340802160079"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,11]]},"references-count":120,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2008,11]]}},"alternative-id":["10.1080\/00016340802160079"],"URL":"https:\/\/doi.org\/10.1080\/00016340802160079","archive":["Portico"],"relation":{},"ISSN":["0001-6349","1600-0412"],"issn-type":[{"value":"0001-6349","type":"print"},{"value":"1600-0412","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,11]]},"assertion":[{"value":"2010-12-31","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}