title: Etiologic heterogeneity in endometrial cancer: evidence from a Gynecologic Oncology Group trial.
abstract: OBJECTIVE
  Although the epidemiology of typical endometrial carcinomas (grades 1-2 endometrioid or Type I) is well established, less is known regarding higher grade endometrioid or non-endometrioid carcinomas (Type II). Within a large Gynecologic Oncology Group trial (GOG-210), which included central pathology review, we investigated the etiologic heterogeneity of endometrial cancers by comparing risk factors for different histologic categories.
  
  
  METHODS
  Based on epidemiologic questionnaire data, risk factor associations, expressed as odds ratios (OR) with 95% confidence intervals (CI), were estimated comparing grade 3 endometrioid and Type II cancers (including histologic subtypes) to grades 1-2 endometrioid cancers.
  
  
  RESULTS
  Compared with 2244 grades 1-2 endometrioid cancers, women with Type II cancers (321 serous, 141 carcinosarcomas, 77 clear cell, 42 mixed epithelial with serous or clear cell components) were older; more often non-white, multiparous, current smokers; and less often obese. Risk factors for grade 3 endometrioid carcinomas (n=354) were generally similar to those identified for Type II cancers, although patients with grade 3 endometrioid tumors more often had histories of breast cancer without tamoxifen exposure while those with Type II tumors were more frequently treated with tamoxifen. Patients with serous cancers and carcinosarcomas more frequently had breast cancer histories with tamoxifen treatment compared to patients with other tumors.
  
  
  CONCLUSIONS
  Risk factors for aggressive endometrial cancers, including grade 3 endometrioid and non-endometrioid tumors, appear to differ from lower grade endometrioid carcinomas. Our findings support etiologic differences between Type I and II endometrial cancers as well as additional heterogeneity within Type II cancers.
authors.affiliation: Hormonal and Reproductive Epidemiology Branch, National Cancer Institute, Rockville, MD 20852, USA. Brintonl@exchange.nih.gov
authors.forename: Louise A
authors.initials: LA
authors.lastname: Brinton
authors.forename: Ashley S
authors.initials: AS
authors.lastname: Felix
authors.forename: D Scott
authors.initials: DS
authors.lastname: McMeekin
authors.forename: William T
authors.initials: WT
authors.lastname: Creasman
authors.forename: Mark E
authors.initials: ME
authors.lastname: Sherman
authors.forename: David
authors.initials: D
authors.lastname: Mutch
authors.forename: David E
authors.initials: DE
authors.lastname: Cohn
authors.forename: Joan L
authors.initials: JL
authors.lastname: Walker
authors.forename: Richard G
authors.initials: RG
authors.lastname: Moore
authors.forename: Levi S
authors.initials: LS
authors.lastname: Downs
authors.forename: Robert A
authors.initials: RA
authors.lastname: Soslow
authors.forename: Richard
authors.initials: R
authors.lastname: Zaino
mesh_terms: D000230:Adenocarcinoma / Q000209:etiology* / Q000473:pathology; D018262:Adenocarcinoma, Clear Cell / Q000209:etiology / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018269:Carcinoma, Endometrioid / Q000209:etiology / Q000473:pathology; D002296:Carcinosarcoma / Q000209:etiology* / Q000473:pathology; D016889:Endometrial Neoplasms / Q000209:etiology* / Q000473:pathology; D005260:Female; D006801:Humans; D016015:Logistic Models; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D016017:Odds Ratio; D012307:Risk Factors; D011795:Surveys and Questionnaires