Dear donors and friends of MERMAID
In the MERMAID Project we want to wish you a merry Christmas and at the same time give you an update of what has happened in the project since the last newsletter in June.
The research in “MERMAID III – The challenge of ovarian cancer: Screening, early diagnosis and the identification of women at high risk” is progressing on schedule.
The goal of the research is to identify one or more methods of diagnosing ovarian cancer at an early stage.
Only around 40% of women diagnosed survive. However, 90% of women diagnosed at an early stage survive, whereas a mere 5-10% survives when diagnosed at a later stage. Hypothetically, via identifying all women at the earliest stage, the survival rate could increase to 90%.
The project is divided into three sub-projects with the aim to identify methods for early diagnosis from a multiple of angles. In the following the Professors in the projects describe what they have focused on in the last six month of 2017.
The project Early detection, screening and long-term survival is headed by Professor Susanne Krüger Kjær, The Dansih Cancer Society, Kræftens Bekæmpelse and Copenhagen University Hospital, Rigshospitalet.
In this sub-project the researchers will established a bio-bank with 200.000 cell samples from the cervix; samples that are taken routinely from all women as they are screened for cervical cancer. Moreover an existing biobank is used that contains samples from 50.000 Danish women. From the samples, cells from the ovaries can be isolated and genetic material can be mapped.
This makes it possible for cancerous cells in the ovaries and their pre-stages to be identified and characterized. A positive result from this project would contribute to enabling the screening of ovarian cancer, in a similar fashion to the way we already screen for cervical cancer.
Ovarian cancer is the leading cause of death among gynaecological malignancies and thus identification of factors influencing the carcinogenesis of this disease would have major public health implications. Antidepressants are widely prescribed among women to treat depression and anxiety disorders, and often as chronical therapy. Some studies have suggested that antidepressants are carcinogenic, however, the evidence is inconsistent. In this part of the Mermaid III project, we identified all women with incident ovarian cancer during 2000-2011 (n?~?4.100 women) and matched each case to around 20 population controls (n?~?59.000 women).
Data on drug use (including tricyclic and related antidepressants, selective serotonin reuptake inhibitors, and other antidepressants), medical and reproductive history and socioeconomic parameters, were obtained from nationwide registries. Compared with non-use, use of selective serotonin reuptake inhibitors was associated with a significantly decreased risk of ovarian cancer, whereas the associations for other antidepressants were close to unity (tricyclic and related antidepressants). Therefore, these results may be implying potential chemopreventive properties of certain antidepressants.
The project Biomarkers and/or prognostic markers is headed by Professor Claus Høgdall, Copenhagen University Hospital, Rigshospitalet.
In this part of the research the scientists investigate the biological material (blood and tissue) from women with ovarian cancer. The most modern techniques are used (molecular analyses) in order to identify biomarkers which are characteristic of the disease.
Biomarkers can be used individually in the disease course. A biomarker can help to detect the cancer early in the disease course, so the patient can be cured. Biomarkers can also help to predict treatment effect, and thus assure that patients can be offered a personal more effective treatment, such as for example biological treatment.
The project is planned to 5-year and divided into 3 sub-studies with a large number of different analyses. The sub-study microRNA is ahead of the planning, while the other two will follow the time schedule. The planned genetic analyses of all known microRNAs have been performed. MicroRNAs are small molecules, which play a very important role in the regulation of genes in the cell. The analyses have already established the basis for three publications and the next is under preparation. Results have been presented at ESGO Congress in Vienna. Analyses of all messenger RNA, which is a type of RNA, which is translated into proteins, is now being performed. The messenger RNA analyses will contribute to more knowledge about microRNAs.
A review- / protocol-article specifically about the biomarkers and/or prognostic markers included in the Mermaid III project have been published. The article describes, among other issues, the genetic aspect of ovarian cancer within the fields of DNA sequencing (a method of determining the order of the four different nucleotides/bases in the DNA molecule (genome), DNA-methylation (determination of the number of methyl groups attached to the DNA molecule which has importance for the regulation of genes/epigenetic) and microRNAs. All three areas are of highest relevance for ovarian cancer and for the identification of new biomarkers that may help to describe future new diagnostic methods and treatments that may contribute to personalized medicine.
The research in the Mermaid III relating to DNA methylation, has been started. There has been established a detailed plan for the project, including the number of patients, selection criteria, the type of samples to be included, types of analyses and the type of relevant statistical methods. The project is planned to find biomarkers for both prediction of chemo-resistance, for diagnostics and for screening. Presently all the biological material has been collected and the methylation analyses are in progress. As basis for the methylation study, a review article is under preparation. It describes the existing knowledge of DNA methylation and ovarian cancer. A large part of the laboratory work will expectedly be completed in 2018.
The third sub-study about DNA sequencing is started up and the first data for description of a very special subtype of the disease are ready for analyses.
Furthermore, has a collaboration been initiated with one of the world’s leading cancer hospitals in the United States, M.D. Anderson, in order to describe a new exciting biomarker.
The Project The infection theory is headed by Professor Jan Blaakær , SDU –University of Southern Denmark, Odense and Odense University Hospital.
The Mermaid research study ”The Infection Theory” has progressed as planned but with a few minor adjustments.
We have published the first paper internationally, ”High-risk HPV is not associated with epithelial ovarian cancer in a Caucasian population”. Infectious Agents and Cancer (2016) 11:39 DOI 10.1186/s13027-016-0087-4
We didn’t expect to demonstrate an etiological correlation between HPV and ovarian cancer, but knowing that HPV virus are causing many different cancers, we needed to examine this to be sure not to overlook a possibly connection.
The following paper dealing with the infection theory is published; Ingerslev K, Hogdall E, Schnack TH, Skovrider-Ruminski W, Hogdall C, Blaakaer J The potential role of infectious agents and pelvic inflammatory disease in ovarian Carcinogenesis. Infectious Agents and Cancer (2017) 12:25 DOI 10.1186/s13027-017-0134-9
In our next paper we have examined the possible role of Cytomegalo-virus (CMV) or Epstein-Barr Virus (EBV) as the infectious microbes transforming peritoneal tissue to ovarian cancer. We did not demonstrate a possible correlation to CMV but we demonstrated a correlation to EBV in 5% of the ovarian cancer cases. Because of these few patients we do have to examine an age-matched control group to be sure not to overlooking a possible connection. The detection of the control group has been a challenge as normal ovaries seldom are removed surgically.
Professor Robert Kurman, John Hopkins Hospital, Baltimore published a possible change in the Fallopian tubes named as ‘carcinoma in situ’ (STIC) and corresponding to the changes preceding cervical cancer. Professor Kurman didn’t explain how these changes might arise, and therefore, we believe that it is of utmost importance to search for an infectious microbe causing carcinoma in situ and ultimately ovarian cancer in the Fallopian tubes.
The completing step in the infection theory is a broader search for the possible microorganism. The time and the technological development have made Next-Generation Sequencing (NGS) affordable. This technique demonstrates the base sequences of DNA and by using this technique we will look for genetic material, or traces of microbes in ovarian cancer tissue. The NGS-study is initiated in the middle of 2017 where we started to choose and compose the panel used for this study.
In all three sub-projects several articles have been published in scientific magazines.
In the spring 2017 the first evaluation of the research in MERMAID III was published. In the evaluation the independent scientific team of experts within the field wrote in the conclusion:
”The research plan is followed and the Mermaid III projects provides new evidence and data on ovarian cancer both in terms of risk factors, screening and early detection, new markers, prognostic factors and potential new treatment options. The very robust scientific environments combined with international collaborators form a promising background for continuous progress ahead.
The projects in the Mermaid III projects have already published several papers indicating that all the parts in projects show expected progress.”
The evaluation is based on a scientific progress report, which the researchers in MERMAID III has written.
The next evaluation will be published in the spring 2018.
The research in MERMAID III is coordinated by professor Bent Ottesen, Project director Rigshospitalet, Copenhagen University Hospital.
Donations and duration
MERMAID III is the MERMAID Project’s largest research project to date with a budget of DKK40 million of which DKK 32.3 has been received in funds and commitments.
We are deeply grateful for all of the donations received to the research.
The research is expected to span over the next seven years.
We look forward to keeping you informed of the progresses of the research.
We thank you for all support and interest in MERMAID and wish you and your families a
Merry Christmas and a happy new year
On behalf of the MERMAID Project
Birgitte Blix Treschow
Project Coordinator, MERMAID