The role of hereditary nonpolyposis colorectal cancer in the management of familial ovarian cancer

• Published in: Genetics in medicine Vol. 8; no. 10; pp. 653 - 657
• Main Authors: Farrell, Carolyn, Lyman, Mollie, Freitag, Katherine, Fahey, Cathy, Piver, M. Steven, Rodabaugh, Kerry J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-10-2006
• Subjects: Colorectal Neoplasms, Hereditary Nonpolyposis - genetics; Female; Genes, BRCA1; Humans; Mutation; Ovarian Neoplasms - epidemiology; Ovarian Neoplasms - genetics; Ovariectomy; Pedigree; Registries; Risk
• ISSN: 1098-3600; 1530-0366
• DOI: 10.1097/01.gim.0000241895.20390.c5

Purpose: Familial ovarian cancer is most often associated with hereditary breast and ovarian cancer, implicating mutations in the BRCA1 and BRCA2 genes. Hereditary nonpolyposis colorectal cancer, another common syndrome, is also associated with ovarian cancer and is caused by DNA mismatch repair genes. We sought to identify the role of hereditary nonpolyposis colorectal cancer in women with family histories of ovarian cancer.
Methods: The likelihood of a genetic syndrome in 226 oophorectomized women in the Gilda Radner Familial Ovarian Cancer Registry was determined by pedigree analysis using clinical criteria and by calculating the probability of a mutation in genes responsible for hereditary breast and ovarian cancer and hereditary nonpolyposis colorectal cancer using available risk models.
Results: Some 86% had a BRCA gene mutation likelihood of 7.8% or higher, warranting consideration of hereditary breast and ovarian cancer. Of the 32 women below this threshold, 4 (12.5%) had family histories that met criteria for clinical diagnosis of hereditary nonpolyposis colorectal cancer. In addition, 16 women (7%) with a BRCA mutation likelihood greater than 7.8% met clinical criteria for hereditary nonpolyposis colorectal cancer or warranted its inclusion in the differential diagnosis. Among all study respondents, 9% had family histories warranting consideration of hereditary nonpolyposis colorectal cancer.
Conclusion: Hereditary nonpolyposis colorectal cancer should be considered in the differential diagnosis of women with family histories of ovarian cancer.