Identification and Molecular Characterization of a New Ovarian Cancer Susceptibility Locus at 17q21.31

Authors

Jennifer Permuth-Wey, Moffitt Cancer Center, Tampa, FL
Kate Lawrenson, University of Southern California, Los Angeles
Howard C. Shen, University of Southern California, Los Angeles
Aneliya Velkova, Moffitt Cancer Center, Tampa, FL
Jonathan P. Tyrer, University of Cambridge
Zhihua Chen, Moffitt Cancer Center, Tampa, FL
Hui-Yi Lin, Moffitt Cancer Center, Tampa, FL
Y. Ann Chen, Moffitt Cancer Center, Tampa, FL
Ya-Yu Tsai, Moffitt Cancer Center, Tampa, FL
Xiaotao Qu, Moffitt Cancer Center, Tampa, FL
Susan J. Ramus, University of Southern California, Los Angeles
Rod Karevan, University of Southern California, Los Angeles
Janet Lee, University of Southern California, Los Angeles
Nathan Lee, University of Southern California, Los Angeles
Melissa C. Larson, Mayo Clinic, Rochester, MN
Katja K. Aben, Radboud University
Hoda Anton-Culver, University of California IrvineFollow
Natalia Antonenkova, Byelorussian Institute for Oncology and Medical Radiology Aleksandrov N.N.
Antonis Antoniou, University of Cambridge
Sebastian M. Armasu, Mayo Clinic, Rochester, MNFollow
Australian Cancer Study, Queensland Institute of Medical Research, Brisbane
Australian Ovarian Cancer Study, Queensland Institute of Medical Research, Brisbane
François Bacot, McGill University and Génome Québec Innovation Centre
Laura Baglietto, University of Melbourne
Elisa V. Bandera, Robert Wood Johnson Medical SchoolFollow
Jill Barnholtz-Sloan, Case Western Reserve University School of Medicine
Matthias W. Beckmann, Friedrich-Alexander-University Erlangen-NurembergFollow
Michael J. Birrer, Massachusetts General Hospital
Greg Bloom, Moffitt Cancer Center, Tampa, FL
Natalia Bogdanova, Hannover Medical School, Hannover, GermanyFollow
Louise A. Brinton, National Cancer Institute, Bethesda MDFollow
Angela Brooks-Wilson, Genome Sciences Centre, BC Cancer Agency, Vancouver, BC, Canada
Robert Brown, Imperial College London, London
Ralf Butzow, University of HelsinkiFollow
Qiuyin Cai, Vanderbilt UniversityFollow
Ian Campbell, University of Melbourne
Jenny Change-Claude, German Cancer Research Center, Heidelberg, Germany
Stephen Chanock, National Cancer Institute, Bethesda MD
Georgia Chenevix-Trench, Queensland Institute of Medical Research, Brisbane, Australia
Jin Q. Cheng, Moffitt Cancer Center, Tampa, FL
Mine S. Cicek, Mayo Clinic College of MedicineFollow
Gerhard A. Coetzee, University of Southern California, Los Angeles
Consortium of Investigators of Modifiers of BRCA1/2
Linda S. Cook, University of New MexicoFollow
Fergus J. Couch, Mayo Clinic, Rochester, MN
Daniel W. Cramer, Brigham and Women's Hospital and Harvard Medical School
Julie M. Cunningham, Mayo Clinic College of Medicine
Agnieszka Dansonka-Mieszkowska, The Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland
Evelyn Despierre, University Hospitals Leuven, Leuven, Belgium
Jennifer Doherty, Dartmouth CollegeFollow

Document Type

Article

Publication Date

7-12-2013

Publication Title

Nature Communications

Abstract

Epithelial ovarian cancer (EOC) has a heritable component that remains to be fully characterized. Most identified common susceptibility variants lie in non-protein-coding sequences. We hypothesized that variants in the 3 ′ untranslated region at putative microRNA (miRNA) binding sites represent functional targets that influence EOC susceptibility. Here, we evaluate the association between 767 miRNA binding site single nucleotide polymorphisms (miRSNPs) and EOC risk in 18,174 EOC cases and 26,134 controls from 43 studies genotyped through the Collaborative Oncological Gene-environment Study. We identify several miRSNPs associated with invasive serous EOC risk (OR=1.12, P =10⁻⁸ ) mapping to an inversion polymorphism at 17q21.31. Additional genotyping of non-miRSNPs at 17q21.31 reveals stronger signals outside the inversion ( P =10⁻¹⁰ ). Variation at 17q21.31 associates with neurological diseases, and our collaboration is the first to report an association with EOC susceptibility. An integrated molecular analysis in this region provides evidence for ARHGAP27 and PLEKHM1 as candidate EOC susceptibility genes.

DOI

10.1038/ncomms2613

Dartmouth Digital Commons Citation

Permuth-Wey, Jennifer; Lawrenson, Kate; Shen, Howard C.; Velkova, Aneliya; Tyrer, Jonathan P.; Chen, Zhihua; Lin, Hui-Yi; Chen, Y. Ann; Tsai, Ya-Yu; Qu, Xiaotao; Ramus, Susan J.; Karevan, Rod; Lee, Janet; Lee, Nathan; Larson, Melissa C.; Aben, Katja K.; Anton-Culver, Hoda; Antonenkova, Natalia; Antoniou, Antonis; Armasu, Sebastian M.; Australian Cancer Study, Queensland Institute of Medical Research, Brisbane; Australian Ovarian Cancer Study, Queensland Institute of Medical Research, Brisbane; Bacot, François; Baglietto, Laura; Bandera, Elisa V.; Barnholtz-Sloan, Jill; Beckmann, Matthias W.; Birrer, Michael J.; Bloom, Greg; Bogdanova, Natalia; Brinton, Louise A.; Brooks-Wilson, Angela; Brown, Robert; Butzow, Ralf; Cai, Qiuyin; Campbell, Ian; Change-Claude, Jenny; Chanock, Stephen; Chenevix-Trench, Georgia; Cheng, Jin Q.; Cicek, Mine S.; Coetzee, Gerhard A.; Consortium of Investigators of Modifiers of BRCA1/2; Cook, Linda S.; Couch, Fergus J.; Cramer, Daniel W.; Cunningham, Julie M.; Dansonka-Mieszkowska, Agnieszka; Despierre, Evelyn; and Doherty, Jennifer, "Identification and Molecular Characterization of a New Ovarian Cancer Susceptibility Locus at 17q21.31" (2013). Dartmouth Scholarship. 2759.
https://digitalcommons.dartmouth.edu/facoa/2759