4.8 Article

Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer

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NATURE GENETICS
卷 49, 期 5, 页码 680-691

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NATURE PORTFOLIO
DOI: 10.1038/ng.3826

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资金

  1. US National Institutes of Health [CA1X01HG007491-01, U19-CA148112, R01-CA149429, R01-CA058598]
  2. Canadian Institutes of Health Research [MOP-86727]
  3. Ovarian Cancer Research Fund
  4. Government of Canada through Genome Canada
  5. Canadian Institutes of Health Research
  6. Ministere de l'Economie, de la Science et de l'Innovation du Quebec through Genome Quebec
  7. Quebec Breast Cancer Foundation
  8. Odense University Hospital Research Foundation
  9. National R&D Program for Cancer Control, Ministry of Health and Welfare, Republic of Korea [1420190]
  10. Italian Association for Cancer Research [IG16933]
  11. German Cancer Aid [110837]
  12. MRC [G0601891] Funding Source: UKRI
  13. Cancer Research UK [20861, 23382, 16561, 16491, 12677, 15973] Funding Source: researchfish
  14. Cancer Research UK
  15. The Francis Crick Institute [10124] Funding Source: researchfish
  16. Medical Research Council [G0601891] Funding Source: researchfish
  17. National Breast Cancer Foundation [PRAC-13-04] Funding Source: researchfish
  18. National Institute for Health Research [NF-SI-0510-10096] Funding Source: researchfish
  19. Ovarian Cancer Action [OCA6] Funding Source: researchfish

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To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3 and 9q31.1) and one for endometrioid EOC (5q12.3). We then performed meta-analysis on the results for high-grade serous ovarian cancer with the results from analysis of 31,448 BRCA1 and BRCA2 mutation carriers, including 3,887 mutation carriers with EOC. This identified three additional susceptibility loci at 2q13, 8q24.1 and 12q24.31. Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a new candidate susceptibility gene for low-grade and borderline serous EOC.

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