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Identification of novel epithelial ovarian cancer loci in women of African ancestry.

Publication ,  Journal Article
Manichaikul, A; Peres, LC; Wang, X-Q; Barnard, ME; Chyn, D; Sheng, X; Du, Z; Tyrer, J; Dennis, J; Schwartz, AG; Cote, ML; Peters, E; Bondy, M ...
Published in: Int J Cancer
June 1, 2020

Women of African ancestry have lower incidence of epithelial ovarian cancer (EOC) yet worse survival compared to women of European ancestry. We conducted a genome-wide association study in African ancestry women with 755 EOC cases, including 537 high-grade serous ovarian carcinomas (HGSOC) and 1,235 controls. We identified four novel loci with suggestive evidence of association with EOC (p < 1 × 10-6 ), including rs4525119 (intronic to AKR1C3), rs7643459 (intronic to LOC101927394), rs4286604 (12 kb 3' of UGT2A2) and rs142091544 (5 kb 5' of WWC1). For HGSOC, we identified six loci with suggestive evidence of association including rs37792 (132 kb 5' of follistatin [FST]), rs57403204 (81 kb 3' of MAGEC1), rs79079890 (LOC105376360 intronic), rs66459581 (5 kb 5' of PRPSAP1), rs116046250 (GABRG3 intronic) and rs192876988 (32 kb 3' of GK2). Among the identified variants, two are near genes known to regulate hormones and diseases of the ovary (AKR1C3 and FST), and two are linked to cancer (AKR1C3 and MAGEC1). In follow-up studies of the 10 identified variants, the GK2 region SNP, rs192876988, showed an inverse association with EOC in European ancestry women (p = 0.002), increased risk of ER positive breast cancer in African ancestry women (p = 0.027) and decreased expression of GK2 in HGSOC tissue from African ancestry women (p = 0.004). A European ancestry-derived polygenic risk score showed positive associations with EOC and HGSOC in women of African ancestry suggesting shared genetic architecture. Our investigation presents evidence of variants for EOC shared among European and African ancestry women and identifies novel EOC risk loci in women of African ancestry.

Duke Scholars

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Published In

Int J Cancer

DOI

EISSN

1097-0215

Publication Date

June 1, 2020

Volume

146

Issue

11

Start / End Page

2987 / 2998

Location

United States

Related Subject Headings

  • White People
  • United States
  • Polymorphism, Single Nucleotide
  • Oncology & Carcinogenesis
  • Neoplasm Proteins
  • Humans
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • Follistatin
  • Female
 

Citation

APA
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Manichaikul, A., Peres, L. C., Wang, X.-Q., Barnard, M. E., Chyn, D., Sheng, X., … African American Cancer Epidemiology Study (AACES) and the Ovarian Cancer Association Consortium (OCAC), . (2020). Identification of novel epithelial ovarian cancer loci in women of African ancestry. Int J Cancer, 146(11), 2987–2998. https://doi.org/10.1002/ijc.32653
Manichaikul, Ani, Lauren C. Peres, Xin-Qun Wang, Mollie E. Barnard, Deanna Chyn, Xin Sheng, Zhaohui Du, et al. “Identification of novel epithelial ovarian cancer loci in women of African ancestry.Int J Cancer 146, no. 11 (June 1, 2020): 2987–98. https://doi.org/10.1002/ijc.32653.
Manichaikul A, Peres LC, Wang X-Q, Barnard ME, Chyn D, Sheng X, et al. Identification of novel epithelial ovarian cancer loci in women of African ancestry. Int J Cancer. 2020 Jun 1;146(11):2987–98.
Manichaikul, Ani, et al. “Identification of novel epithelial ovarian cancer loci in women of African ancestry.Int J Cancer, vol. 146, no. 11, June 2020, pp. 2987–98. Pubmed, doi:10.1002/ijc.32653.
Manichaikul A, Peres LC, Wang X-Q, Barnard ME, Chyn D, Sheng X, Du Z, Tyrer J, Dennis J, Schwartz AG, Cote ML, Peters E, Moorman PG, Bondy M, Barnholtz-Sloan JS, Terry P, Alberg AJ, Bandera EV, Funkhouser E, Wu AH, Pearce CL, Pike M, Setiawan VW, Haiman CA, African American Breast Cancer Consortium (AABC), African Ancestry Prostate Cancer Consortium (AAPC), Palmer JR, LeMarchand L, Wilkens LR, Berchuck A, Doherty JA, Modugno F, Ness R, Moysich K, Karlan BY, Whittemore AS, McGuire V, Sieh W, Lawrenson K, Gayther S, Sellers TA, Pharoah P, Schildkraut JM, African American Cancer Epidemiology Study (AACES) and the Ovarian Cancer Association Consortium (OCAC). Identification of novel epithelial ovarian cancer loci in women of African ancestry. Int J Cancer. 2020 Jun 1;146(11):2987–2998.
Journal cover image

Published In

Int J Cancer

DOI

EISSN

1097-0215

Publication Date

June 1, 2020

Volume

146

Issue

11

Start / End Page

2987 / 2998

Location

United States

Related Subject Headings

  • White People
  • United States
  • Polymorphism, Single Nucleotide
  • Oncology & Carcinogenesis
  • Neoplasm Proteins
  • Humans
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • Follistatin
  • Female