ArticleNature communications2013
Epigenetic analysis leads to identification of HNF1B as a subtype-specific susceptibility gene for ovarian cancer.
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Article in Nature communications, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers, 5 of them syntheses that pooled it.
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105citing papers in PubMed, 5 pooled it
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Who cites it
105 citing papers in PubMed, 5 syntheses or guidelines pooled it, 169 citations in OpenAlex.
- Cumulative evidence for relationships between multiple variants of HNF1B and the risk of prostate and endometrial cancers.BMC medical genetics · 2018Pooled it
- A splicing variant of TERT identified by GWAS interacts with menopausal estrogen therapy in risk of ovarian cancer.International journal of cancer · 2016Pooled it
- Pooled it
- Common variants at the CHEK2 gene locus and risk of epithelial ovarian cancer.Carcinogenesis · 2015Pooled it
- Network-Based Integration of GWAS and Gene Expression Identifies a HOX-Centric Network Associated with Serous Ovarian Cancer Risk.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2015Pooled it
- Candidate locus analysis of the TERT-CLPTM1L cancer risk region on chromosome 5p15 identifies multiple independent variants associated with endometrial cancer risk.Human genetics · 2015Trial
- Differentially methylated loci distinguish ovarian carcinoma histological types: evaluation of a DNA methylation assay in FFPE tissue.BioMed research international · 2013Trial
- Immunological and prognostic impact of NRF2 in high grade serous ovarian cancer.Genes and immunity · 2026Article
- Genome-wide association study of 398,238 women unveils seven loci associated with high-grade serous ovarian cancer.NPJ genomic medicine · 2025Article
- Molecular Pathology of Ovarian Endometrioid Carcinoma: A Review.Oncology research · 2025Review
- Integrated multi-omics analysis reveals clinical significance of hepatocyte nuclear factor-1β in tumor immune microenvironment, immunotherapy and prognostic prediction for colon adenocarcinoma.Cancer immunology, immunotherapy : CII · 2024Article
- Utilization of immunohistochemistry in gynecologic tumors: An expert review.Gynecologic oncology reports · 2024Review
- Integrative multi-omics analyses to identify the genetic and functional mechanisms underlying ovarian cancer risk regions.American journal of human genetics · 2024Article
- Cell State of Origin Impacts Development of Distinct Endometriosis-Related Ovarian Carcinoma Histotypes.Cancer research · 2024Article
- Clinicopathological characteristics, molecular features and novel diagnostic strategies for the detection of malignant transformation of endometriosis (Review).Experimental and therapeutic medicine · 2023Review
- Exploring genetic loci of type 2 diabetes and cancer: a review.Endocrine oncology (Bristol, England) · 2023Review
- Extensive germline-somatic interplay contributes to prostate cancer progression through HNF1B co-option of TMPRSS2-ERG.Nature communications · 2022Article
- Copy Number Variants Are Ovarian Cancer Risk Alleles at Known and Novel Risk Loci.Journal of the National Cancer Institute · 2022Article
- Reference Module-Based Analysis of Ovarian Cancer Transcriptome Identifies Important Modules and Potential Drugs.Biochemical genetics · 2022Article
- Functional analysis of the 1p34.3 risk locus implicates GNL2 in high-grade serous ovarian cancer.American journal of human genetics · 2022Article
45 more citing papers are in PubMed but not listed here.
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Authors and funding
171 authors at 20 institutions in 15 countries.
Hui ShenUSC Epigenome Center, Keck School of Medicine, University of Southern California, Norris Comprehensive Cancer Center, Los Angeles, California 90033, USA.
Brooke L Fridley
Honglin Song
Kate Lawrenson
Julie M Cunningham
Susan J Ramus
Mine S Cicek
Jonathan Tyrer
Douglas Stram
Melissa C Larson
Martin Köbel
PRACTICAL Consortium
Argyrios Ziogas
Wei Zheng
Hannah P Yang
Anna H Wu
Eva L Wozniak
Yin Ling Woo
Boris Winterhoff
Elisabeth Wik
Alice S Whittemore
Nicolas Wentzensen
Rachel Palmieri Weber
Allison F Vitonis
Daniel Vincent
Robert A Vierkant
Ignace Vergote
David Van Den Berg
Anne M Van Altena
Shelley S Tworoger
Pamela J Thompson
Daniel C Tessier
Kathryn L Terry
Soo-Hwang Teo
Claire Templeman
Daniel O Stram
Melissa C Southey
Weiva Sieh
Nadeem Siddiqui
Yurii B Shvetsov
Xiao-Ou Shu
Viji Shridhar
Shan Wang-Gohrke
Gianluca Severi
Ira Schwaab
Helga B Salvesen
Iwona K Rzepecka
Ingo B Runnebaum
Mary Anne Rossing
Lorna Rodriguez-Rodriguez
Harvey A Risch
Stefan P Renner
Elizabeth M Poole
Malcolm C Pike
Catherine M Phelan
Liisa M Pelttari
Tanja Pejovic
James Paul
Irene Orlow
Siti Zawiah Omar
Sara H Olson
Kunle Odunsi
Stefan Nickels
Heli Nevanlinna
Roberta B Ness
Steven A Narod
Toru Nakanishi
Kirsten B Moysich
Alvaro N A Monteiro
Joanna Moes-Sosnowska
Francesmary Modugno
Usha Menon
John R McLaughlin
Valerie McGuire
Keitaro Matsuo
Noor Azmi Mat Adenan
Leon F A G Massuger
Galina Lurie
Lene Lundvall
Jan Lubiński
Jolanta Lissowska
Douglas A Levine
Arto Leminen
Alice W Lee
Nhu D Le
Sandrina Lambrechts
Diether Lambrechts
Jolanta Kupryjanczyk
Camilla Krakstad
Gottfried E Konecny
Susanne Krüger Kjaer
Lambertus A Kiemeney
Linda E Kelemen
Gary L Keeney
Beth Y Karlan
Rod Karevan
Kimberly R Kalli
Hiroaki Kajiyama
Bu-Tian Ji
Allan Jensen
Anna Jakubowska
Edwin Iversen
Satoyo Hosono
Claus K Høgdall
Estrid Høgdall
Maureen Hoatlin
Peter Hillemanns
Florian Heitz
Rebecca Hein
Philipp Harter
Mari K Halle
Per Hall
Jacek Gronwald
Martin Gore
Marc T Goodman
Graham G Giles
Aleksandra Gentry-Maharaj
Montserrat Garcia-Closas
James M Flanagan
Peter A Fasching
Arif B Ekici
Robert Edwards
Diana Eccles
Douglas F Easton
Matthias Dürst
Andreas du Bois
Thilo Dörk
Jennifer A Doherty
Evelyn Despierre
Agnieszka Dansonka-Mieszkowska
Cezary Cybulski
Daniel W Cramer
Linda S Cook
Xiaoqing Chen
Bridget Charbonneau
Jenny Chang-Claude
Ian Campbell
Ralf Butzow
Clareann H Bunker
Doerthe Brueggmann
Robert Brown
Angela Brooks-Wilson
Louise A Brinton
Natalia Bogdanova
Matthew S Block
Elizabeth Benjamin
Jonathan Beesley
Matthias W Beckmann
Elisa V Bandera
Laura Baglietto
François Bacot
Sebastian M Armasu
Natalia Antonenkova
Hoda Anton-Culver
Katja K Aben
Dong Liang
Xifeng Wu
Karen Lu
Michelle A T Hildebrandt
Australian Ovarian Cancer Study Group
Australian Cancer Study
Joellen M Schildkraut
Thomas A Sellers
David Huntsman
Andrew Berchuck
Georgia Chenevix-Trench
Simon A Gayther
Paul D P Pharoah
Peter W Laird
Ellen L Goode
Celeste Leigh Pearce
University of Southern California · USMayo Clinic · USBrigham and Women's Hospital · USMayo Clinic in Florida · USThe Maria Sklodowska-Curie National Research Institute of Oncology · PLThe University of Melbourne · AUBC Cancer Agency · CAHaukeland University Hospital · NOInternational Hereditary Cancer Center · PLKU Leuven · BEMoffitt Cancer Center · USNational Cancer Institute · USRadboud University Nijmegen · NLUniversity College London · GBUniversity of Cambridge · GBUniversity of Helsinki · FIAichi Cancer Center · JPCopenhagen University Hospital · DKGenome Canada · CAGerman Cancer Research Center · DE
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Elisa de Stanchina · 1985 to 2026
$347.4MUSC/NORRIS COMPREHENSIVE CANCER CENTER (CORE) SUPPORTP30CA014089 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Saul Priceman · 1985 to 2026
$181.4MWomen's Cancer ProgramP30CA015083 · NCI · MAYO CLINIC ROCHESTER · PI Keith L. Knutson · 1985 to 2026
$151.3MTwo-Spirit Films in Indigenous Cancer HealthP30CA016056 · NCI · ROSWELL PARK CANCER INSTITUTE CORP · PI Christine B. Ambrosone · 1985 to 2026
$116.6MHormone-Related CancersZIACP010126 · NCI · DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS · PI GIERACH, GRETCHEN · 2009 to 2025
$103.5MTRANSCRIPTIONAL PROFILINGP30CA072720 · NCI · UNIV OF MED/DENT NJ-R W JOHNSON MED SCH · PI Shridar Ganesan · 1997 to 2026
$94.5MUniversity of Hawaii Cancer Center CCSGP30CA071789 · NCI · UNIVERSITY OF HAWAII AT MANOA · PI Xin Chen · 1996 to 2026
$56.2MUse of microfluidic tumor cultures to enable clinical trials of therapies for ovarian cancerP50CA136393 · NCI · MAYO CLINIC ROCHESTER · PI SCOTT H KAUFMANN · 2009 to 2026
$37.0MRisk Factors for Breast Cancer in Younger NursesR01CA050385 · NCI · HARVARD UNIVERSITY (SCH OF PUBLIC HLTH) · PI ELIASSEN, A. HEATHER, WILLETT, WALTER C. · 1989 to 2019
$32.3MWITHIN SUBJ VARIABILITY IN MEASUREMENTS DRUG METABOL ENZYMES IN HLTY SUBJM01RR000056 · NCRR · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI LEVINE, ARTHUR S · 1985 to 2006
$29.2MNorthern California Cooperative Family Registry for Breast CancerU01CA069417 · NCI · NORTHERN CALIFORNIA CANCER CENTER · PI JOHN, ESTHER M. · 1995 to 2010
$22.4MUSC CANCER EPIDEMIOLOGY &BIOSTATISTICS UNITP01CA017054 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI DEAPEN, DENNIS M. · 1985 to 2009
$18.2MCancer Research UK 10118Cancer Research UK 10124Cancer Research UK 11022Cancer Research UK 13086Cancer Research UK 14136Cancer Research UK 15960Cancer Research UK 16561Cancer Research UK C490/A10119Cancer Research UK C490/A10124Cancer Research UK C490/A6187Cancer Research UK C536/A13086Cancer Research UK C536/A6689CIHR MOP-86727CIHR MSH-87734Intramural NIH HHSMedical Research Council G0401527Medical Research Council G1000143NCI NIH HHS K07 CA080668NCI NIH HHS K07 CA092044NCI NIH HHS K07 CA095666NCI NIH HHS K07-CA095666NCI NIH HHS K07 CA143047NCI NIH HHS K07-CA143047NCI NIH HHS K07-CA80668NCI NIH HHS K22 CA138563NCI NIH HHS K22-CA138563NCI NIH HHS N01 CN025403NCI NIH HHS N01-CN25403NCI NIH HHS N01-CN55424NCI NIH HHS N01 PC035137NCI NIH HHS N01-PC035137NCI NIH HHS N01-PC067001NCI NIH HHS P01 CA017054NCI NIH HHS P01-CA017054NCI NIH HHS P01-CA087696NCI NIH HHS P30 CA008748NCI NIH HHS P30 CA014089NCI NIH HHS P30 CA015083NCI NIH HHS P30 CA016056NCI NIH HHS P30 CA071789NCI NIH HHS P30-CA15083NCI NIH HHS P50 CA105009NCI NIH HHS P50-CA105009NCI NIH HHS P50 CA136393NCI NIH HHS P50-CA136393NCI NIH HHS R01-CA014089NCI NIH HHS R01-CA016056NCI NIH HHS R01-CA017054NCI NIH HHS R01 CA049449NCI NIH HHS R01-CA049449NCI NIH HHS R01 CA050385NCI NIH HHS R01-CA050385NCI NIH HHS R01 CA054419NCI NIH HHS R01-CA054419NCI NIH HHS R01 CA058598NCI NIH HHS R01-CA058598NCI NIH HHS R01 CA058860NCI NIH HHS R01-CA058860NCI NIH HHS R01-CA061107NCI NIH HHS R01-CA061132NCI NIH HHS R01 CA063682NCI NIH HHS R01 CA064277NCI NIH HHS R01-CA064277NCI NIH HHS R01 CA067262NCI NIH HHS R01-CA067262NCI NIH HHS R01-CA071766NCI NIH HHS R01 CA074850NCI NIH HHS R01-CA074850NCI NIH HHS R01 CA076016NCI NIH HHS R01-CA076016NCI NIH HHS R01 CA080742NCI NIH HHS R01-CA080742NCI NIH HHS R01-CA080978NCI NIH HHS R01 CA083918NCI NIH HHS R01 CA087538NCI NIH HHS R01-CA087538NCI NIH HHS R01 CA087696NCI NIH HHS R01-CA092044NCI NIH HHS R01 CA096958NCI NIH HHS R01 CA106414NCI NIH HHS R01-CA106414NCI NIH HHS R01 CA112523NCI NIH HHS R01-CA112523NCI NIH HHS R01 CA114343NCI NIH HHS R01-CA114343NCI NIH HHS R01 CA122443NCI NIH HHS R01-CA122443NCI NIH HHS R01 CA126841NCI NIH HHS R01-CA126841NCI NIH HHS R01 CA141154NCI NIH HHS R01-CA141154NCI NIH HHS R01 CA149429NCI NIH HHS R01-CA149429NCI NIH HHS R01CA83918NCI NIH HHS R03 CA113148NCI NIH HHS R03-CA113148NCI NIH HHS R03 CA115195NCI NIH HHS R03-CA115195NCI NIH HHS R25 CA092049NCI NIH HHS R37 CA070867NCI NIH HHS R37-CA070867NCI NIH HHS R37-CA70867NCI NIH HHS U01 CA069417NCI NIH HHS U01-CA069417NCI NIH HHS U01-CA071966NCI NIH HHS U19 CA148112NCI NIH HHS U19-CA148112NCI NIH HHS U24 CA143882NCRR NIH HHS M01 RR000056NCRR NIH HHS M01-RR000056NIGMS NIH HHS T32 GM067587NIGMS NIH HHS T32GM067587Wellcome TrustWellcome Trust 076113
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 polymorphisms associate with invasive serous (rs7405776 odds ratio (OR)=1.13, P=3.1 × 10(-10)) and clear cell (rs11651755 OR=0.77, P=1.6 × 10(-8)) epithelial ovarian cancer. Risk alleles for the serous subtype associate with higher HNF1B-promoter methylation in these tumours. Unmethylated, expressed HNF1B, primarily present in clear cell tumours, coincides with a CpG island methylator phenotype affecting numerous other promoters throughout the genome. Different variants in HNF1B associate with risk of serous and clear cell epithelial ovarian cancer; DNA methylation and expression patterns are also notably distinct between these subtypes. These findings underscore distinct mechanisms driving different epithelial ovarian cancer histological subtypes.
Indexed as
Epigenesis, GeneticGenetic Predisposition to DiseaseDNA MethylationFemaleGene Expression ProfilingHepatocyte Nuclear Factor 1-betaHumansOvarian NeoplasmsPolymorphism, Single NucleotidePromoter Regions, GeneticHepatocyte Nuclear Factor 1-betaHNF1B protein, human
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