Uterine Serous Carcinoma: Increased Familial Risk for Lynch-Associated Malignancies
- 1 March 2012
- journal article
- Published by American Association for Cancer Research (AACR) in Cancer Prevention Research
- Vol. 5 (3), 435-443
- https://doi.org/10.1158/1940-6207.capr-11-0499
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. Cancer Prev Res; 5(3); 435–43. ©2012 AACR.Keywords
Other Versions
This publication has 46 references indexed in Scilit:
- Contribution of germline mutations in the BRCA and PALB2 genes to pancreatic cancer in ItalyFamilial Cancer, 2011
- Prevalence of BRCA1 and BRCA2 mutations in Ashkenazi Jewish families with breast and pancreatic cancerCancer, 2011
- PARP Inhibitors in Cancer Therapy: Promise, Progress, and PuzzlesCancer Cell, 2011
- Exomic Sequencing Identifies PALB2 as a Pancreatic Cancer Susceptibility GeneScience, 2009
- Prevalence and characteristics of pancreatic cancer in families with BRCA1 and BRCA2 mutationsFamilial Cancer, 2008
- Hereditary gynecologic cancers: differential diagnosis, surveillance, management and surgical prophylaxisFamilial Cancer, 2007
- High incidence of BRCA1–2 germline mutations, previous breast cancer and familial cancer history in Jewish patients with uterine serous papillary carcinomaEuropean Journal of Surgical Oncology, 2006
- Association between uterine serous carcinoma and breast cancerGynecologic Oncology, 2004
- Is Uterine Papillary Serous Adenocarcinoma a Manifestation of the Hereditary Breast–Ovarian Cancer Syndrome?Gynecologic Oncology, 2000
- A Familial Syndrome of Pancreatic Cancer and Melanoma with a Mutation in theCDKN2Tumor-Suppressor GeneNew England Journal of Medicine, 1995