Newsletter summer 2017

Dear donors and friends of MERMAID

At the MERMAID Project we would like to wish  you a pleasant summer and provide an update of the development of the project since January.


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 is described what the researchers have focused on in the first six month of 2017.


The project Early detection and longer survival is headed by Professor Susanne Krüger Kjær, The Dansih Cancer Society, Kræftens Bekæmpelse and Copenhagen University Hospital, Rigshospitalet.

Ovarian cancer is the most lethal gynecologic cancer in the developed world and it most often has a poor prognosis. As we still have many gaps in our knowledge about ovarian cancer etiology, it is important to identify risk factors.
We are currently investigating several potential risk factors for ovarian cancer. For example, pelvic inflammatory disease (PID) was associated with an increased risk of borderline ovarian tumors (a potential precursor of ovarian cancer), particularly among women who had had multiple episodes of PID. Although our results indicated a histotype-specific association with PID, the association of PID with ovarian cancer risk is still somewhat uncertain and requires further investigation.
We are also currently investigating other potential risk factors such as family history of cancer in the ovary/breast, endometriosis, and infertility.


The project Biomarkers and/or prognostic markers is headed by professor Claus Høgdall, Rigshospitalet.

In this part of the research scientists investigate the biological material (blood and tissue) from women with ovarian cancer. The most advanced techniques (molecular analyses) are used to identify biomarkers, which are characteristic of the disease.

A biomarker can help to detect cancer early in the disease course, so that the patient can be cured. Using a biomarker that can predict the treatment effect, patients may be offered a personal more effective treatment as for example biological treatment.

The project is divided into a large number of sub-studies with planned analyses over a timetable of five years. The timetable is followed overall, but has successfully been brought forward for planned genetic analysis of microRNA before timetable (MicroRNA are small molecules, which play a very important role in the regulation of genes in the cell). Ahead of schedule, it has thus been possible to produce several scientific publications.

A summary/protocol-article specifically dealing with biomarkers and/or prognostic markers of Mermaid III project is finished and will within a few weeks be submitted for publication. The article describes, among other things, the genetic aspect of ovary cancer within the fields of DNA sequencing (method for determining the order of the four different nucleotides / bases (building blocks) in the DNA molecule (inherited mass), DNA-methylation (determination of the number of methyl groups coupled to the DNA molecule that is important for the regulation of the genes / epigenetic) and microRNAs.

All three areas are of highest relevance for ovary cancer and for the identification of new biomarkers and the development of treatment for the purposes of personalized medicine. The article will be sent into the scientific journal “Contemporary Clinical Trials” as a first priority.

The research in the Mermaid III relating to DNA methylation, has begun. There has been established a detailed plan for the project, including the number of patients, selection criteria, the type of samples to be included, type of analyses and the type of relevant statistical calculations. The project is planned in such a way that we have the opportunity to find biomarkers for both prediction of chemo-resistance, for diagnosis and screening.


The Project The infection theory is headed by Professor Jan Blaakær , SDU –University of Southern Denmark, Odense and Odense University Hospital.

Epithelial ovarian cancer (EOC) has a high mortality due to the late onset of symptoms and the resulting disseminated disease at diagnosis.  Almost 90% of all ovarian cancers originate from epithelial cells and historically these were thought to arise from the surface mesothelial lining of the ovaries.
However, recent research has indicated that a large proportion of serous EOC could originate in precancerous lesions called serous tubal intraepithelial carcinomas (STICs) located in the fimbriated end of the fallopian tubes.

There is an increasing focus on the role of infectious agents in human carcinogenesis. It is estimated that 20% of the global cancer burden is attributed to infectious causes. In view of the lacking understanding of EOC etiology, and the fact that the female internal genitalia are directly accessible to outside pathogens, it is relevant to consider a potential role of infectious agents in ovarian carcinogenesis.


Therefore, we have up till now published the following papers:

  1. 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

2. Ingerslev K, Hogdall E, Skovrider-Ruminski W,  Schnack TH, Aarenstrup Karlsen M, Nedergaard L, Hogdall C, Blaakær J.

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

The first paper is reviewing the literature about infectious agents and EOC. In the second paper, we demonstrated, that HPV is not the cause of EOC.
All extractions of DNA for the rest of the study have been performed and a paper dealing with cytomegalovirus (CMV) is soon ready for publication.

Our next study is the Next Generation Sequencing study examining for an infectious agent in the STIC’s. This study is performed in collaboration with Dr. Joseph W. Carlson, Dept. of Oncology-Pathology, Karolinska Institutet and Dept. of Pathology, Karolinska University Hospital.

These studies are part of a Ph.D. study carried out by Kasper Ingerslev, MD, at the University of Southern Denmark.

To supplement our studies hitherto, we have planned a study of the vaginal microbiome together with guest professor Ronnie Lamont, the University of Edinburgh, in the late 2017.

In all three sub-projects several articles have been published in scientific journals.

Evaluation

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 research

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 75 % 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 six 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 pleasant summer!

Kind regards,
on behalf of the MERMAID Project

Birgitte Blix Treschow,
adm. project coordinator, MERMAID