title: Uterine serous carcinoma: increased familial risk for lynch-associated malignancies.
abstract: Serous uterine cancer is not a feature of any known hereditary cancer syndrome. This study evaluated familial risk of cancers for patients with serous uterine carcinoma, focusing on Lynch syndrome malignancies. Fifty serous or mixed serous endometrial carcinoma cases were prospectively enrolled. Pedigrees were developed for 29 probands and tumors were assessed for DNA mismatch repair (MMR) abnormalities. Standardized incidence ratios for cancers in relatives were estimated. A second-stage analysis was undertaken using data from Gynecologic Oncology Group (GOG)-210. Incidence data for cancers reported in relatives of 348 patients with serous and mixed epithelial and 624 patients with endometrioid carcinoma were compared. Nineteen of 29 (65.5%) patients in the single-institution series reported a Lynch-related cancer in relatives. Endometrial and ovarian cancers were significantly overrepresented and a high number of probands (6 of 29, 20.7%) reported pancreatic cancers. None of the probands' tumors had DNA MMR abnormalities. There was no difference in endometrial or ovarian cancer incidence in relatives of serous and endometrioid cancer probands in the case-control study. Pancreatic cancers were, however, significantly more common in relatives of patients with serous cancer [OR, 2.39; 95% confidence interval (CI), 1.06-5.38]. We identified an excess of endometrial, ovarian, and pancreatic cancers in relatives of patients with serous cancer in a single-institution study. Follow-up studies suggest that only pancreatic cancers are overrepresented in relatives. DNA MMR defects in familial clustering of pancreatic and other Lynch-associated malignancies are unlikely. The excess of pancreatic cancers in relatives may reflect an as yet unidentified hereditary syndrome that includes uterine serous cancers.
authors.affiliation: Department of Obstetrics and Gynecology, Washington University School of Medicine, 660 South Euclid, St. Louis, MO 63110, USA.
authors.forename: Summer B
authors.initials: SB
authors.lastname: Dewdney
authors.forename: Nora T
authors.initials: NT
authors.lastname: Kizer
authors.forename: Abegail A
authors.initials: AA
authors.lastname: Andaya
authors.forename: Sheri A
authors.initials: SA
authors.lastname: Babb
authors.forename: Jingqin
authors.initials: J
authors.lastname: Luo
authors.forename: David G
authors.initials: DG
authors.lastname: Mutch
authors.forename: Amy P
authors.initials: AP
authors.lastname: Schmidt
authors.forename: Louise A
authors.initials: LA
authors.lastname: Brinton
authors.forename: Russell R
authors.initials: RR
authors.lastname: Broaddus
authors.forename: Nilsa C
authors.initials: NC
authors.lastname: Ramirez
authors.forename: Phyllis C
authors.initials: PC
authors.lastname: Huettner
authors.forename: Donald Scott
authors.initials: DS
authors.lastname: McMeekin
authors.forename: Kathleen
authors.initials: K
authors.lastname: Darcy
authors.forename: Shamshad
authors.initials: S
authors.lastname: Ali
authors.forename: Patricia L
authors.initials: PL
authors.lastname: Judson
authors.forename: Robert S
authors.initials: RS
authors.lastname: Mannel
authors.forename: Shashikant B
authors.initials: SB
authors.lastname: Lele
authors.forename: David M
authors.initials: DM
authors.lastname: O'Malley
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Goodfellow
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000209:etiology*; D018284:Cystadenocarcinoma, Serous / Q000150:complications*; D053843:DNA Mismatch Repair / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D009386:Neoplastic Syndromes, Hereditary / Q000235:genetics*; D010375:Pedigree; D011379:Prognosis; D011446:Prospective Studies; D014594:Uterine Neoplasms / Q000150:complications*