Biomarkers of Cancer: Biocomputional analysis of data from population-based biobanks and health registries
We have demonstrated that miRNAs can be successfully isolated from the Janus serum samples, with funding from the BIOBANK programme. Biocomputational analyses based on combined data from miRNA sequencing, detailed cancer registry data and environmental exposure data from health surveys, will generate new knowledge in cancer research.
About the project
-
Project period: 01.04.2016 - 31.05.2030 (Active)
- Coordinating Institution: Norwegian Institute of Public Health
-
Project Manager:
- Hilde Langseth, Norwegian Institute of Public Health
-
Project Participants:
- Eckart Meese, Universität des Saarlandes
- Andreas Keller, Universität des Saarlandes
Summary
Over 30,000 Norwegians develop cancer each year, and cancer is the second most common cause of death in the country. Breast cancer is the most common form of cancer in women and prostate cancer in men, followed by colorectal cancer and lung cancer in both sexes. Tools to detect cancer at an early stage, and thereby improve survival, are very important. In this project, we will use miRNA profiles from prediagnostic serum samples from the Janus Serum Bank in combination with information about cancer from the Cancer Registry and information about environmental exposure from health surveys in advanced bioinformatic and biostatistical analyses. The purpose of the study is to investigate whether these profiles can be used as early markers for colorectal cancer and lung cancer. miRNAs are small non-coding RNAs with a size of approximately 22 nucleotides. They play a central role in the initiation and progression of cancer. We will also sequence a large number of Janus samples from breast and prostate cancer patients.
Background
Little is known about circulating miRNA expression prior to cancer diagnosis. The dynamics of differential miRNA expression with regards to cancer onset and progression are undetermined. We propose to profile miRNA expression dynamics in order to determine when, relative to diagnosis, and with what confidence, carcinogenesis can be detected.
Most studies on miRNA and cancer have shown differential miRNA expression in tissue samples collected at time of diagnosis, and several promising diagnostic miRNA biomarkers have been identified. However, also these studies have typically been small, with 10-100 patients. These results support the idea that serum-derived miRNAs can be valuable biomarkers of cancer. Studies on circulating miRNA have so far been small, often with less than 100 patients. No study, that we are aware of, has had the statistical power to identify differentially expressed circulating miRNA and produce an in-depth understanding of circulating miRNA in context of different subtypes and aggressiveness of the cancer. However, circulating miRNA at the time of diagnosis, selectively released by malignant cells, can differentiate between cancer and healthy controls3 . In this proposal, with substantially larger sample size, we will evaluate and expand on these results.
Project aims
- Build biocomputational expertise to handle large scale biomarker and exposure data
- Assess the significance of small non-coding RNAs as early biomarkers of cancer
- Model the relationship between biomarkers, exposure and cancer occurrence
- Explore the translational potential of biomarkers of cancer
WP 1 Project management, coordination and ethical, legal and social aspects (ELSA) WP leader: Langseth Co-leaders: Ursin, Weiderpass Co-investigators: Andreassen, Gislefoss, Rounge and in addition for ELSA: Olav and Solberg
Overall aims:
- Ensure that the project is managed efficiently and according to all applicable laws
- Further develop common national and international ELSA standards in biobank and registry based research
WP 2 small non-coding RNA as early detection biomarkers of cancer WP leader: Rounge, co-leader: Andreassen, Co-investigators: 2 postdocs, Frigessi, Gislefoss, Grimsrud, Grotmol, Hovig, Kjærheim, Langseth, Leidinger, Lyle, Meese, Nothnagel, Stram, Tretli, Ursin,Vos, Weiderpass
Overall aim: Evaluate small non-coding RNAs as early detection biomarkers of cancer
WP 3 Environmental exposures and biomarkers of cancer WP leader Langseth Co leader Andreassen Co-investigators: 1 post doc, Frigessi, Gislefoss, Grimsrud, Kjærheim, Nothnagel, Rounge, Stram, Tretli, Ursin, Weiderpass
Aims:
- Investigate the effect of exposure data from health surveys on all cancers and subtype specific cancer risk in the entire Janus cohort (~70000 cancer cases, 300000 individuals in total).
- Investigate the role of the following on miRNA expression levels (~3000 cases LC, CRC, BC, PC, TGCT): 1) Exposure data from health surveys 2) Existing biomarkers from earlier research projects in the Janus cohort
- Model the complex interplay between miRNA expression and environmental risk factors with respect to cancer