Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Apr;8(4):1875-1881.
doi: 10.1002/cam4.2000. Epub 2019 Mar 1.

Association between family history, mutation locations, and prevalence of BRCA1 or 2 mutations in ovarian cancer patients

Christian F Singer  1 , Yen Y Tan  1 , Daniela Muhr  1 , Christine Rappaport  1 , Daphne Gschwantler-Kaulich  1 , Christoph Grimm  1 , Stephan Polterauer  1 , Georg Pfeiler  1 , Andreas Berger  1 , Muy-Kheng M Tea  1
Affiliations

Association between family history, mutation locations, and prevalence of BRCA1 or 2 mutations in ovarian cancer patients

Christian F Singer et al. Cancer Med. 2019 Apr.

Abstract

We investigated the prevalence of germline BRCA mutations in a population-based cohort of Austrian women diagnosed with ovarian cancer and its association with family history of cancer. We prospectively collected family pedigrees of 443 Austrian ovarian cancer patients who had been tested for the presence of a germline BRCA or 2 mutations and correlated the familial breast and ovarian cancer burden with the prevalence of BRCA mutations and disease onset. The probability of carrying a gBRCA mutation in patients without family history of cancer is 14% (95% CI 9%-22%), as opposed to 45% (95% CI 31%-59%) of patients with at least one family member with ovarian cancer, and 47% (95% CI 40%-54%) if other relatives have developed breast cancer. If both breast and ovarian cancer are diagnosed in the family, the probability of carrying a germline BRCA1 or 2 mutations is 60% (95% CI 50%-68%). germline BRCA1 or mutations in families with ovarian cancer only are commonly located in the Ovarian Cancer Cluster Regions when compared to families with both breast and ovarian cancer (P = 0.001, and P = 0.020, respectively). While gBRCA mutation carriers with ovarian cancer do not have a significantly different age at onset than patients with a family history of cancer, gBRCA1 carriers in general have an earlier onset than gBRCA2 carriers (P = 0.002) and patients without a mutation (P = 0.006). The rate of germline BRCA1 or 2 mutations in ovarian cancer patients without a family history or breast or ovarian cancer is low. However, in women with additional family members affected, the prevalence is considerably higher than previously reported.

Keywords: BRCA; family history; mutation locations; ovarian cancer; pedigree.

PubMed Disclaimer

Conflict of interest statement

None.

Figures

Figure 1
Figure 1
Prevalence of germline BRCA1 (dark gray) and 2 (light gray) mutations and wild‐type BRCA (WT, white) in OC patients with: (1) no additional OC or BC in family; (2) at least one additional OC in family; (3) no additional OC but at least one BC in family; (4) at least one additional OC and at least one BC in family
Figure 2
Figure 2
(A) Prevalence of BRCA1 mutation in relation to their respective Ovarian Cancer Cluster Region (OCCR). (B) Prevalence of BRCA2 mutation in relation to their respective OCCRs
Figure 3
Figure 3
Age at diagnosis in OC patients with (1) no additional OC or BC in family; (2) at least one additional OC in family; (3) no additional OC but at least one BC in family; (4) at least one additional OC and at least one BC in family
Figure 4
Figure 4
Age at diagnosis of OC patients with a BRCA1, BRCA2 germline mutation, and in women without a BRCA germline mutation
See this image and copyright information in PMC

References

    1. Antoniou A, Pharoah PD, Narod S, et al. Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case Series unselected for family history: a combined analysis of 22 studies. Am J Hum Genet. 2003;72:1117‐1130. - PMC - PubMed
    1. Levy‐Lahad E, Friedman E. Cancer risks among BRCA1 and BRCA2 mutation carriers. Br J Cancer. 2007;96:11‐15. - PMC - PubMed
    1. Pal T, Permuth‐Wey J, Betts JA, et al. BRCA1 and BRCA2 mutations account for a large proportion of ovarian carcinoma cases. Cancer. 2005;104:2807‐2816. - PubMed
    1. Alsop K, Fereday S, Meldrum C, et al. BRCA mutation frequency and patterns of treatment response in BRCA mutation‐positive women with ovarian cancer: a report from the Australian Ovarian Cancer Study Group. J Clin Oncol. 2012;30:2654‐2663. - PMC - PubMed
    1. Shanmughapriya S, Nachiappan V, Natarajaseenivasan K. BRCA1 and BRCA2 mutations in the ovarian cancer population across race and ethnicity: special reference to Asia. Oncology. 2013;84:226‐232. - PubMed

Publication types