Epigenetic Analysis Leads to Identification of HNF1B as a Subtype-Specific Susceptibility Gene for Ovarian Cancer
Hui Shen;Brooke Fridley;Honglin Song;Kate Lawrenson;Julie Cunningham;Susan Ramus;Mine Cicek;Jonathan Tyrer;Douglas Stram;Melissa Larson;Martin Köbel;PRACTICAL Consortium;Argyrios Ziogas;Wei Zheng;Hannah Yang;Anna Wu;Eva Wozniak;Yin Ling Woo;Boris Winterhoff;Elisabeth Wik;Alice Whittemore;Nicolas Wentzensen;Rachel Palmieri Weber;Allison Vitonis;Daniel Vincent;Robert Vierkant;Ignace Vergote;David Van Den Berg;Anne M. Van Altena;Shelley Tworoger;Pamela Thompson;Daniel Tessier;Kathryn Terry;Soo-Hwang Teo;Claire Templeman;Daniel Stram;Melissa Southey;Weiva Sieh;Nadeem Siddiqui;Yurii Shvetsov;Xiao-Ou Shu;Viji Shridhar;Shan Wang-Gohrke;Gianluca Severi;Ira Schwaab;Helga Salvesen;Iwona Rzepecka;Ingo Runnebaum;Mary Anne Rossing;Lorna Rodriguez-Rodriguez;Harvey Risch;Stefan Renner;Elizabeth Poole;Malcolm Pike;Catherine Phelan;Liisa Pelttari;Tanja Pejovic;James Paul;Irene Orlow;Siti Zawiah Omar;Sara Olson;Kunle Odunsi;Stefan Nickels;Heli Nevanlinna;Roberta Ness;Steven Narod;Toru Nakanishi;Kirsten Moysich;Alvaro N.A. Monteiro;Joanna Moes-Sosnowska;Francesmary Modugno;Usha Menon;John McLaughlin;Valerie McGuire;Keitaro Matsuo;Noor Azmi Mat Adenan;Leon F.A. G. Massuger;Galina Lurie;Lene Lundvall;Jan Lubiński;Jolanta Lissowska;Douglas Levine;Arto Leminen;Alice Lee;Nhu Le;Sandrina Lambrechts;Diether Lambrechts;Jolanta Kupryjanczyk;Camilla Krakstad;Gottfried Konecny;Susanne Krüger Kjaer;Lambertus Kiemeney;Linda Kelemen;Gary Keeney;Beth Karlan;Rod Karevan;Kimberly Kalli;Hiroaki Kajiyama;Bu-Tian Ji;Allan Jensen
Abstract
HNF1B is overexpressed in clear cell epithelial ovarian cancer, and we observed epigenetic silencing in serous epithelial ovarian cancer, leading us to hypothesize that variation in this gene differentially associates with epithelial ovarian cancer risk according to histological subtype. Here we comprehensively map variation in HNF1B with respect to epithelial ovarian cancer risk and analyse DNA methylation and expression profiles across histological subtypes. Different single-nucleotide polymor