UK Ovarian Cancer Population Study

Overview

Although up to 10% of women diagnosed with ovarian cancer have genetic predisposition to the cancer, the remaining 90% are sporadic cases. The latter women are likely to have some genetic factors that will predispose them to the disease but until recently there was very little evidence for this. UKOPS has contributed to the international Ovarian Cancer Association Consortium (OCAC), an amalgamation of 47 groups from around the world and identified several of these factors that only increase the risks marginally compared to the BRCA1/2 mutations in the women at ‘high risk’ to answer the question ‘Why do some women develop ovarian cancer and not others?”.

Currently, CA125 is the only marker used for detecting ovarian cancer early and monitoring its course. The effort through UKOPS has been to identify novel markers that could aid CA125.

Symptoms for ovarian cancer are vague and non-specific and therefore it is difficult to identify the women who have ovarian cancer in primary care. UKOPS is exploring which symptoms or medical complaints are common in women with ovarian cancer when compared to women who do not have the disease.

centres

Patient Information Sheet [link to PDF]

Design/ Intervention

Case control study

Objectives/ Aims

Primary

To establish a case control series for:

  • Detection of genes with moderate penetrance for ovarian cancer using single nucleotide polymorphisms (SNP study)
  • Assessment of biomarker profile of ovarian cancer cases pre, post-op and following chemotherapy (Biomarker study)
  • Identification of which symptoms or medical complaints are common in women with ovarian cancer when compared to women who do not have the disease (Symptoms study)

Secondary

  • Build a model of individualised ovarian cancer risk rediction based on the genetic and biomarker profiles
  • To establish a serum bank for future assessment of novel tumour markers

Subjects

1200 confirmed primary epithelial ovarian cancer cases of which 300 are recruited pre-operativey
500 benign/borderline neoplasm
2800 healthy controls

Inclusion/ Exclusion Criteria

Exclusion criteria for healthy controls (no exclusion criteria for the cases) - History of bilateral oophorectomy

Recruitment

Cases

  1. Women with an adnexal mass suspicious of ovarian cancer who are about to undergo surgery
  2. Women with a confirmed diagnosis of primary invasive or borderline ovarian cancer
  3. Women with a probable diagnosis of primary invasive ovarian cancer who are not undergoing surgery

Controls

  1. Women with a possible benign or borderline adnexal mass who are about to undergo surgery
  2. Apparently healthy women recruited from the Multimodal arm of UKCTOCS when they attend for annual screening

Funding

The Eve Appeal

The Oak Foundation

NIHR Centre

Bio Bank

Consists of plasma, serum,DNA, formalin fixed paraffin embedded (FFPE) blocks

Study Duration

2 years

Investigators

Prof Usha Menon
Chief Investigator (UCL)
Dr Aleksandra Gentry-Maharaj Co-Investigator (UCL)

Research Team (UCL)

Dr Andy Ryan
Senior Data Manager
Robert Liston
Senior Software Analyst
Chloe Karpinskyj
Research Assistant
Nyala Balogun
Senior Research Nurse
Anita Lim
PhD Student

Administration Team

Tracy Roberts
Administrator

Laboratory Team

Jeremy Ford
Laboratory Manager
Richard Gunu
Bio Medical Scientist
Nuno Alvez
Medical Laboratory Assistant
Josie Cunningham
Medical Laboratory Assistant
Kristin Tamm
Medical Laboratory Assistant

Centres

UCLH / Barts
University College Hospital and Bart’s Hospital, London

Prof Usha Menon (PI),  Nyala Balogun
Bristol
St Michael’s Hospital

Mr John Murdoch (PI), Carole Shahin,
Elizabeth Patch
East Kent
Queen Elizabeth the Queen Mother Hospital, Margate

Mr Andy Nordin (PI),  Linda Davies
Southend
Southend Hospital


Mr Khalil Razvi, Gemma Ogden
Portsmouth
St. Mary’s Hospital

Mr Rob Woolas (PI),  Mary Anderson
Gateshead
Queen Elizabeth Hospital

Mr Keith Godfrey (PI), Rachael Mugnai, Gerri Thompson
North Wales
Llandudno General Hospital and Ysbyty Gwynedd

Mr Simon Leeson (PI),  Denise Longley, Carol Chapman
Manchester
St. Mary’s Hospital and Wellcome Clinical Research Facility

Mr Mourad Seif (PI), Sue Renshaw, Domini Mullins
Belfast
Belfast City Hospital

Mr Stephen Dobbs (PI),  Adrina O’Donnell, Margaret Murray
Middlesbrough
James Cook University Hospital


Mr Derek Cruickshank (PI), Jane McNeil

Publications

  • Celeste Leigh Pearce et al. on behalf of the Ovarian Cancer Association Consortium. No evidence of gene-environment interactions with confirmed ovarian cancer risk factors:  joint effects by histological subtype (in press, CEBP)
  • Jennifer Permuth-Wey1 et al. Identification and molecular characterization of a new ovarian cancer susceptibility locus at 17q21.31 (In press, Nature Communications)
  • Shen H et al. Epigenetic Analysis Leads to Identification of HNF1B as a Subtype-Specific Susceptibility Gene for Ovarian Cancer (In press, Nature Communications)
  • Faber MT et a.l Cigarette smoking and risk of ovarian cancer - a pooled analysis of 21 case-control studies xxx
  • Olsen C et al. on behalf of the Ovarian Cancer Association Consortium. Obesity and risk of ovarian cancer subtypes: evidence from the Ovarian Cancer Association Consortium.
  • Bojesen SE et al. Multiple independent TERT variants associated with telomere length and risks of breast and ovarian cancer (Nature Genetics, in press)
  • Pharoah PDP et al. GWAS meta-analysis and replication identifies three new susceptibility loci for ovarian cancer. (Nature Genetics, in press)
  • Lu Y et al. Genome-wide association study for ovarian cancer susceptibility using pooled DNA. Twin Res Hum Genet 2012;15(5):615-23.
  • Pearce CL et al. on behalf of the Ovarian Cancer Association Consortium Association between endometriosis and risk of histological subtypes of ovarian cancer: a pooled analysis of case-control studies. Lancet Oncol 2012;13(4):385-94.
  • Fridley BL et al. Gene set analysis of survival following ovarian cancer implicates macrolide binding and intracellular signaling genes Cancer epidemiology, biomarkers & prevention: a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2012. 21(3): p. 529-36.
  • Beesley J et al. Functional polymorphisms in the TERT promoter are associated with risk of serous epithelial ovarian and breast cancers. PloS one, 2011. 6(9): p. e24987.
  • Permuth-Wey J et al. on behalf of the Ovarian Cancer Association Consortium (OCAC). 2011. MicroRNA Processing and Binding Site Polymorphisms are not Replicated in the Ovarian Cancer Association Consortium. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2011. 20(8): p. 1793-7.
  • Lurie G et al. The Australian Ovarian Cancer Study and Australian Cancer Study Groups, Goodman MT; The Ovarian Cancer Association Consortium. Estrogen Receptor Beta rs1271572 Polymorphism and Invasive Ovarian Carcinoma Risk: Pooled Analysis within the Ovarian Cancer Association Consortium. PloS one, 2011. 6(6): p. e20703.
  • Terry KL et al. A polymorphism in the GALNT2 gene and ovarian cancer risk in four population based case-control studies. Int J Mol Epidemiol Genet;1(4):272-7.
  • Amankwah EK et al. on behalf of the Ovarian Cancer Association Consortium. Polymorphisms in stromal genes and susceptibility to serous epithelial ovarian cancer: a report from the Ovarian Cancer Association Consortium.PloS one, 2011. 6(5): p. e19642.
  • Permuth-Wey J et al. LIN28B polymorphisms influence susceptibility to epithelial ovarian cancer. Cancer Res 2011;71(11):3896-903.
  • Amankwah EK et al. on behalf of the Ovarian Cancer Association Consortium. Prostate cancer susceptibility polymorphism rs2660753 is not associated with invasive ovarian cancer Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2011. 20(5): p. 1028-31.
  • Pearce CL et al. Genetic variation in insulin-like growth factor 2 may play a role in ovarian cancer risk. Hum Mol Genet 2011;20(11):2263-72.
  • Pharoah PDP et al. Ovarian Cancer Association Consortium, Consortium of Investigators of Modifiers of BRCA1/2, Andrew Berchuck, Harvey A. Risch The role of KRAS rs61764370 in invasive epithelial ovarian cancer: implications for clinical testing. Clinical cancer research : an official journal of the American Association for Cancer Research, 2011. 17(11): p. 3742-50.
  • Bolton EL et al. Australian Ovarian Canc Study Grp, and Australian Canc Study Ovarian Canc, and Ovarian Canc Assoc Consortium, (2010) Common variants at 19p13 are associated with susceptibility to ovarian cancer. Nature genetics, 2010. 42(10): p. 880-4.
  • Lose F et al. Vascular endothelial growth factor gene polymorphisms and ovarian cancer survival. Gynecologic oncology, 2010. 119(3): p. 479-83.
  • Goode EL et al. on behalf of the Ovarian Cancer Association Consortium (OCAC) A Genome-Wide Association Study Identifies Susceptibility Loci for Ovarian Cancer at 2q31 and 8q24. Nature genetics, 2010. 42(10): p. 874-9.
  • Near AM et al. on behalf of the Ovarian Cancer Association Consortium. Progesterone Receptor Gene Polymorphisms and Risk of Endometriosis:  Results from an International Collaborative Effort. Fertility and sterility, 2011. 95(1): p. 40-5.
  • Notaridou M et al. on behalf of the Ovarian Cancer Association Consortium Common Alleles In Candidate Susceptibility Genes Associated With Risk And Development Of Epithelial Ovarian Cancer International journal of cancer. Journal international du cancer, 2011. 128(9): p. 2063-74.
  • Johnatty SE et al. Ovarian Cancer Association Consortium. Evaluation of candidate stromal epithelial cross-talk genes identifies association between risk of serous ovarian cancer and TERT, a cancer susceptibility "hot-spot”. PLoS genetics, 2010. 6(7): p. e1001016.
  • Kelemen et al. on behalf of the Ovarian Cancer Association Consortium. Genetic Variation in TYMS in the One-Carbon Transfer Pathway Is Associated with Ovarian Carcinoma Types in the Ovarian Cancer Association Consortium Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2010. 19(7): p. 1822-30.
  • Lurie G et al. on behalf of the Ovarian Cancer Association Consortium. Vitamin D receptor rs2228570 polymorphism and invasive ovarian carcinoma risk: pooled analysis in five studies within the Ovarian Cancer Association Consortium. International journal of cancer. Journal international du cancer, 2011. 128(4): p. 936-43.
  • Doherty JA et al. on behalf of the Ovarian Cancer Association Consortium (OCAC) ESR1/SYNE1 polymorphism and invasive epithelial ovarian cancer risk: an Ovarian Cancer Association Consortium study. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2010. 19(1): p. 245-50.
  • Cunningham JM et al. Cell cycle genes and ovarian cancer susceptibility: a tagSNP analysis. British journal of cancer, 2009. 101(8): p. 1461-8.
  • Song H et al. A Genome-Wide Association Study Identifies A Novel Ovarian Cancer Susceptibility Locus On 9p22.2. Nature genetics, 2009. 41(9): p. 996-1000.
  • Song H et al. on behalf of the Ovarian Cancer Association Consortium (OCAC) Association between invasive ovarian cancer susceptibility and 11 best candidate SNPs from breast cancer genome-wide association study. Human molecular genetics, 2009. 18(12): p. 2297-304.
  • Quaye L et al. Tagging Single Nucleotide Polymorphisms In Candidate Oncognenes And Susceptibility To Ovarian Cancer. British journal of cancer, 2009. 100(6): p. 993-1001.
  • Quaye L et al. Functional Complementation Studies Identify Candidate Genes and Common Genetic Variants Associated with Ovarian Cancer Survival. Human molecular genetics, 2009. 18(10): p. 1869-78.
  • Pearce CL et al. on behalf of the Ovarian Cancer Association Consortium. Validating genetic risk associations for ovarian cancer through the international Ovarian Cancer Association Consortium.British journal of cancer, 2009. 100(2): p. 412-20.
  • Palmieri RT et al. Polymorphism in the IL18 gene and epithelial ovarian cancer in non-Hispanic white women. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2008. 17(12): p. 3567-72.
  • Ramus SJ et al on behalf of the Ovarian Cancer Association.Consortium (OCAC) Consortium Analysis of 7 Candidate SNPs for Ovarian Cancer. International journal of cancer. Journal international du cancer, 2008. 123(2): p. 380-8.

Conference presentations

Poster presentation on “The Ovarian Tumour Tissue Array (OTTA) Consortium” Ramus SJ, Kobel M, Dafou D, Benjamin EC, Wozniak E, Hogdall E, Kruger Kjaer S, Christensen L, Sowter HM, Al-Attar A, Edmondson R, Darby S, Chivukula M, Kalli K, Elliott E, Kalloger SE, Driver K, Widschwendter M, Gentry-Maharaj A, Menon U, Jacobs IJ, Wentzensen N, Sherman M, Garcia-Closas M, Fasching PA, Chenevix-Trench G, Berchuck A, Ovarian Cancer Association Consortium, Bowtell D, Whittemore AS, Pharoah PDP, Ness R, Goode EL, Huntsman DG, Gayther SA.

Page last modified on 09 jun 13 21:19