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
. 2015 Sep 10;33(26):2901-7.
doi: 10.1200/JCO.2015.61.2408. Epub 2015 Aug 10.

Contribution of Germline Mutations in the RAD51B, RAD51C, and RAD51D Genes to Ovarian Cancer in the Population

Honglin Song  1 , Ed Dicks  1 , Susan J Ramus  1 , Jonathan P Tyrer  1 , Maria P Intermaggio  1 , Jane Hayward  1 , Christopher K Edlund  1 , David Conti  1 , Patricia Harrington  1 , Lindsay Fraser  1 , Susan Philpott  1 , Christopher Anderson  1 , Adam Rosenthal  1 , Aleksandra Gentry-Maharaj  1 , David D Bowtell  1 , Kathryn Alsop  1 , Mine S Cicek  1 , Julie M Cunningham  1 , Brooke L Fridley  1 , Jennifer Alsop  1 , Mercedes Jimenez-Linan  1 , Estrid Høgdall  1 , Claus K Høgdall  1 , Allan Jensen  1 , Susanne Krüger Kjaer  1 , Jan Lubiński  1 , Tomasz Huzarski  1 , Anna Jakubowska  1 , Jacek Gronwald  1 , Samantha Poblete  1 , Shashi Lele  1 , Lara Sucheston-Campbell  1 , Kirsten B Moysich  1 , Kunle Odunsi  1 , Ellen L Goode  1 , Usha Menon  1 , Ian J Jacobs  1 , Simon A Gayther  2 , Paul D P Pharoah  1
Affiliations

Contribution of Germline Mutations in the RAD51B, RAD51C, and RAD51D Genes to Ovarian Cancer in the Population

Honglin Song et al. J Clin Oncol. .

Abstract

Purpose: The aim of this study was to estimate the contribution of deleterious mutations in the RAD51B, RAD51C, and RAD51D genes to invasive epithelial ovarian cancer (EOC) in the population and in a screening trial of individuals at high risk of ovarian cancer.

Patients and methods: The coding sequence and splice site boundaries of the three RAD51 genes were sequenced and analyzed in germline DNA from a case-control study of 3,429 patients with invasive EOC and 2,772 controls as well as in 2,000 unaffected women who were BRCA1/BRCA2 negative from the United Kingdom Familial Ovarian Cancer Screening Study (UK_FOCSS) after quality-control analysis.

Results: In the case-control study, we identified predicted deleterious mutations in 28 EOC cases (0.82%) compared with three controls (0.11%; P < .001). Mutations in EOC cases were more frequent in RAD51C (14 occurrences, 0.41%) and RAD51D (12 occurrences, 0.35%) than in RAD51B (two occurrences, 0.06%). RAD51C mutations were associated with an odds ratio of 5.2 (95% CI, 1.1 to 24; P = .035), and RAD51D mutations conferred an odds ratio of 12 (95% CI, 1.5 to 90; P = .019). We identified 13 RAD51 mutations (0.65%) in unaffected UK_FOCSS participants (RAD51C, n = 7; RAD51D, n = 5; and RAD51B, n = 1), which was a significantly greater rate than in controls (P < .001); furthermore, RAD51 mutation carriers were more likely than noncarriers to have a family history of ovarian cancer (P < .001).

Conclusion: These results confirm that RAD51C and RAD51D are moderate ovarian cancer susceptibility genes and suggest that they confer levels of risk of EOC that may warrant their use alongside BRCA1 and BRCA2 in routine clinical genetic testing.

PubMed Disclaimer

Conflict of interest statement

Authors' disclosures of potential conflicts of interest are found in the article online at www.jco.org. Author contributions are found at the end of this article.

Figures

Fig 1.
Fig 1.
Distribution of predicted deleterious variants in RAD51B, RAD51C, and RAD51D. The location of each mutation is shown in the exon structure of the coding sequence. Mutations occurring in multiple individuals are indicated with the number of carriers above the small balloon. Coding regions of all the genes are on the same scale. (*) Deleterious mutation identified (one each in case and control groups). bp, base pair.
See this image and copyright information in PMC

References

    1. Jervis S, Song H, Lee A, et al. Ovarian cancer familial relative risks by tumour subtypes and by known ovarian cancer genetic susceptibility variants. J Med Genet. 2014;51:108–113. - PubMed
    1. Stratton JF, Pharoah P, Smith SK, et al. A systematic review and meta-analysis of family history and risk of ovarian cancer. Br J Obstet Gynaecol. 1998;105:493–499. - PubMed
    1. Lichtenstein P, Holm NV, Verkasalo PK, et al. Environmental and heritable factors in the causation of cancer: Analyses of cohorts of twins from Sweden, Denmark, and Finland. N Engl J Med. 2000;343:78–85. - PubMed
    1. Wooster R, Bignell G, Lancaster J, et al. Identification of the breast cancer susceptibility gene BRCA2. Nature. 1995;378:789–792. - PubMed
    1. Gayther SA, Harrington P, Russell P, et al. Rapid detection of regionally clustered germ-line BRCA1 mutations by multiplex heteroduplex analysis: UKCCCR Familial Ovarian Cancer Study Group. Am J Hum Genet. 1996;58:451–456. - PMC - PubMed

Publication types