Background: Endometrial and ovarian cancers are the sixth and seventh most common cancers in women worldwide.1 Inherited germline mutations in genes such as BRCA1 and BRCA2 have been identified in 6% to 24% of women with gynecologic cancers.2-4 The identification of mutations in gynecologic cancer susceptibility genes in healthy women may allow more personalized cancer risk management, surveillance, chemopreventive approaches, and/or prophylactic surgeries. For women already diagnosed with a gynecologic cancer, the identification of mutations may provide potential targets for biologic agents and guide treatment decisions.
Objectives: Here we describe the demographics and characteristics of 324 individuals with a self-reported diagnosis of ovarian and/or endometrial cancer who received a 30-gene panel genetic test for hereditary cancer risk.
Methods: These 324 patients were referred for hereditary cancer testing by their healthcare provider. All patient demographic information was collected via a self-reported online health history questionnaire.
Results: In this cohort, the median reported age at cancer diagnosis was 53 and 54 years for ovarian and endometrial cancers, respectively. Overall, a total of 49 individuals were found to carry a single pathogenic or likely pathogenic mutation in 1 of the 30 genes tested, and 4 individuals were found to carry 2 concurrent pathogenic mutations. Notably, 24 of the 57 mutations identified were reported in the BRCA1 and BRCA2 genes, yielding an overall BRCA1 and BRCA2 mutation rate of 7.4%. In total, a pathogenic mutation was identified in 12 of the 30 genes, including several genes with known ovarian/endometrial cancer risks (BRCA1, BRCA2, BRIP1, MLH1, MSH2, PALB2, RAD51C, and RAD51D), as well as some genes with less established gynecologic cancer risk (ATM and CHEK2). In addition, 3 patients—2 ovarian cancer patients and 1 endometrial cancer patient—were found to carry a single pathogenic mutation in MUTYH, and 3 ovarian cancer patients and 1 endometrial cancer patient were found to carry the APC c.3920T>A (I1307K) mutation. Because neither of these genes have previously been associated with increased ovarian/endometrial cancer risk, these mutations are considered incidental findings and are unlikely to be the cause of the patient’s disease.
Conclusions: In summary, the overall mutation carrier rate in this cohort for known breast/ovarian cancer risk genes was 10.8% (35/324). Taken together, these data support the recommendation that all patients with gynecologic cancers should undergo broad germline testing for hereditary cancer risk.
Disclosure: This work was sponsored by Color Genomics.
- Ferlay J, Soerjomataram I, Ervik M, et al. GLOBOCAN 2012 v1.1. Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11. Lyon, France: International Agency for Research on Cancer; 2013. http://globocan.iarc.fr. Accessed January 16, 2015.
- Walsh T, Casadei S, Lee MK, et al. Mutations in 12 genes for inherited ovarian, fallopian tube, and peritoneal carcinoma identified by massively parallel sequencing. Proc Natl Acad Sci U S A. 2011;108:18032-18037.
- Susswein LR, Marshall ML, Nusbaum R, et al. Pathogenic and likely pathogenic variant prevalence among the first 10,000 patients referred for next-generation cancer panel testing. Genet Med. 2015;18:823-832.
- LaDuca H, Stuenkel AJ, Dolinsky JS, et al. Utilization of multigene panels in hereditary cancer predisposition testing: analysis of more than 2,000 patients. Genet Med. 2014;16:830-837.