Identification of six new susceptibility loci for invasive epithelial ovarian cancer

Karoline Kuchenbaecker, Susan Ramus, Jonathan Tyrer, Andrew Lee, Howard Shen, Jonathan Beesley, Kate Lawrenson, Lesley McGuffog, Sue Healey, Janet Lee, Scott Grist

    Research output: Contribution to journalArticle

    143 Citations (Scopus)

    Abstract

    Genome-wide association studies (GWAS) have identified 12 epithelial ovarian cancer (EOC) susceptibility alleles. The pattern of association at these loci is consistent in BRCA1 and BRCA2 mutation carriers who are at high risk of EOC. After imputation to 1000 Genomes Project data, we assessed associations of 11 million genetic variants with EOC risk from 15,437 cases unselected for family history and 30,845 controls and from 15,252 BRCA1 mutation carriers and 8,211 BRCA2 mutation carriers (3,096 with ovarian cancer), and we combined the results in a meta-analysis. This new study design yielded increased statistical power, leading to the discovery of six new EOC susceptibility loci. Variants at 1p36 (nearest gene, WNT4), 4q26 (SYNPO2), 9q34.2 (ABO) and 17q11.2 (ATAD5) were associated with EOC risk, and at 1p34.3 (RSPO1) and 6p22.1 (GPX6) variants were specifically associated with the serous EOC subtype, all with P < 5 × 10 â+'8. Incorporating these variants into risk assessment tools will improve clinical risk predictions for BRCA1 and BRCA2 mutation carriers.

    Original languageEnglish
    Pages (from-to)164-171
    Number of pages8
    JournalNature Genetics
    Volume47
    Issue number2
    DOIs
    Publication statusPublished - 2015

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  • Cite this

    Kuchenbaecker, K., Ramus, S., Tyrer, J., Lee, A., Shen, H., Beesley, J., Lawrenson, K., McGuffog, L., Healey, S., Lee, J., & Grist, S. (2015). Identification of six new susceptibility loci for invasive epithelial ovarian cancer. Nature Genetics, 47(2), 164-171. https://doi.org/10.1038/ng.3185