Fredrik Wiklund

This project aims to further advance the understanding of inherited genetic determinants for prostate cancer (PCa) aggressiveness and prognosis. To achieve this, we will apply large-scale genomic assessments in several study populations of PCa in collaboration with international research groups. Genome-wide association studies of individual genetic variants and combined effects of genetic risk scores will be explored. In addition, gene expression imputation to perform transcriptome-wide association studies will be applied. Through this approach, we enable a comprehensive assessment of inherited genomic variants with respect to PCa aggressiveness and prognosis. Of importance, the clinical translatability of identified genetic markers will be investigated. The proposed project has the possibility to contribute to considerable advancement in the understanding of the underlying etiology of the development of aggressive disease and disease progression, as well as improving the clinical management of this disease.

This project aims to further develop the understanding of the importance of inherited genetic factors for the prognosis of prostate and testicular cancers. To achieve this, we will apply comprehensive genetic investigations in several study populations of prostate and testicular cancer in collaboration with international research groups. We will examine individual genetic variants as well as combined effects of several genetic variants. We will also investigate the expression of genes and its significance for the prognosis of these cancers. This project will enable a comprehensive assessment of inherited genetic variants significance for recurrence in prostate cancer patients who have undergone radical prostatectomy. For testicular cancer, an improved understanding of the genetic significance for the emergence of this tumor form is expected, as well as an improved accuracy in recurrence detection.

RNA expression and genetic variants in the causal estimation of endometrial cancer risk - a mendelian randomization study<br/><br/>NOResearch stay abroadEndometrial cancer is the most common gynecological cancer in the Western world. It is known that obesity is the most important risk factor. In this study, we will analyze the genetic background in serum samples from patients with endometrial cancer to understand the importance of genetics and RNA expression in the development of the disease.The incidence of endometrial cancer is increasing, and is currently the most common gynecological cancer in the Western world. It is known that obesity is the most important risk factor. In this study, we will analyze the genetic background in serum samples from patients with endometrial cancer to understand the importance of genetics and RNA expression in the development of the disease.<br/>We have genotyped serum samples from 320 patients with endometrial cancer, who have provided a blood sample to the Janus serum bank up to 11 years prior to diagnosis, and an equally large control group. From the same sample, we have produced RNA sequencing data. We investigate whether there is a causal relationship between RNA and risk of uterine cancer by controlling for the part of the variation in RNA that is due to genetic variation (Mendelian randomization). In-depth analysis will provide new insight into the processes involved in the development of uterine cancer. The project is a collaboration between the Norwegian Cancer Registry, OUS Cancer Clinic, University of Bergen, Norwegian Sequencing Center and Karolinska Institutet in Sweden as well as researchers from the National Cancer Institute, USA<br/><br/>In 2024, the focus of the project has been to identify the association between SNPs and pre-diagnostic circulating miRNA levels. Some of the preliminary findings of this analysis were presented at the Mendelian Randomization Conference in Bristol (see bullet point 2 below). Given the complexity of molecular data in MRI, the selection of the optimal set of SNPs requires the performance of a colocalization analysis to confirm the validity of the SNPs as good instruments in MRI. These analyses are now ongoing to identify the best-fitting SNPs. In the next phase of the project, we will focus on finalizing the SNP selection and performing a two-sample MR analysis by integrating JanusRNA data with publicly available datasets from endometrial cancer patients, to improve the power and robustness of the analyses. <br/><br/>The postdoc in the project has actively contributed to the following conferences/meetings and guidance in 2024:<br/>• Endometrial cancer collaborating project meeting with all collaborating partners nationally and internationally (Oslo, June 3-4, 2024) – Assistance in <br/> organizing the meeting and presentation of the latest findings and updates related to the study. Mendelian Randomization Conference (Bristol University, UK, June 19-21, 2024) – Selected speaker. Association of the Nordic Cancer Registries (ANCR) Symposium 2024 (Bodø, August 28-31, 2024) – Abstract evaluation committee. session).<br/>• Supervision of a master's thesis student at the University of Oslo (Informatics - Programming and System Architecture). Thesis topic: Application of <br/> machine learning techniques for colorectal cancer prediction.<br/><br/>Upcoming publications<br/>• The results showing the associations between SNPs and small RNAs will be published as a separate work, focusing on the identification of expression quantitative trait loci (eQTL) and their impact on small RNA expression levels.<br/>• A second paper will present the findings from the MR analysis, using the identified RNA associations to assess their causal role in endometrial cancer risk.<br/><br/>In 2024, the Postdoc in the project has participated in the publication of two articles on gynaecological cancer (see research product) and contributed as a resource in a side project on the validation of miRNA as an early marker for lung cancer (manuscript submitted with the postdoc as first author).<br/>

In Sweden, about 2,400 men die annually due to prostate cancer. Patients with an early prostate cancer diagnosis usually undergo treatment with the aim of curing the disease. Because the side effects of active treatment are significant, it is important to find new markers for aggressive forms of prostate cancer that can differentiate those who are most in need of curative treatment. We intend to conduct large-scale genetic tests in blood samples from men with prostate cancer. The significance of genetic differences detected between men with aggressive disease compared to men with a good prognosis will be studied. Our hope is to identify new genetic markers for prostate cancer that can predict the clinical course, so that those patients who are most in need of treatment aimed at cure are offered such.

In Sweden, about 2,400 men die annually due to prostate cancer. Patients with an early prostate cancer diagnosis usually undergo treatment with the aim of curing the disease. Because the side effects of active treatment are significant, it is important to find new markers for aggressive forms of prostate cancer that can differentiate those who are most in need of curative treatment. We intend to conduct large-scale genetic tests in blood samples from men with prostate cancer. The significance of genetic differences detected between men with aggressive disease compared to men with a good prognosis will be studied. Our hope is to identify new genetic markers for prostate cancer that can predict the clinical course, so that those patients who are most in need of treatment aimed at cure are offered such.

In Sweden, about 2,500 men die each year due to cancer in the prostate. Patients with an early prostate cancer diagnosis usually undergo a treatment aimed at curing the disease. Since the side effects of active treatment are significant, it is important to find new markers for aggressive forms of prostate cancer that can distinguish those most in need of curative treatment. We intend to carry out large-scale genetic studies in blood samples from men with prostate cancer. The significance of genetic differences discovered between men who die in their disease compared to men with good prognosis will be verified in independent populations. Our hope is to identify new genetic markers for prostate cancer that can predict the clinical course, so that the patients who are in greatest need of treatment for cure are offered such.

In Sweden, about 2,500 men die each year due to cancer in the prostate. Patients with an early prostate cancer diagnosis usually undergo a treatment aimed at curing the disease. Since the side effects of active treatment are significant, it is important to find new markers for aggressive forms of prostate cancer that can distinguish those most in need of curative treatment. We intend to carry out large-scale genetic studies in blood samples from men with prostate cancer. The significance of genetic differences discovered between men who die in their disease compared to men with good prognosis will be verified in independent populations. Our hope is to identify new genetic markers for prostate cancer that can predict the clinical course, so that the patients who are in greatest need of treatment for cure are offered such.

In Sweden, about 2,500 men die each year due to cancer in the prostate. Patients with an early prostate cancer diagnosis usually undergo a treatment aimed at curing the disease. Since the side effects of active treatment are significant, it is important to find new markers for aggressive forms of prostate cancer that can distinguish those most in need of curative treatment. We intend to carry out large-scale genetic studies in blood samples from men with prostate cancer. The significance of genetic differences discovered between men who die in their disease compared to men with good prognosis will be verified in independent populations. Our hope is to identify new genetic markers for prostate cancer that can predict the clinical course, so that the patients who are in greatest need of treatment for cure are offered such.

In Sweden, about 2,500 men die each year due to cancer in the prostate. Patients with an early prostate cancer diagnosis usually undergo a treatment aimed at curing the disease. Since the side effects of active treatment are significant, it is important to find new markers for aggressive forms of prostate cancer that can distinguish those most in need of curative treatment. Testicular cancer is the most common form of cancer in young men. Relatives of men with testicular cancer are at significantly increased risk of suffering from this type of cancer, indicating a strong genetic component of this disease. We intend to carry out genetic and molecular studies in blood samples from healthy men and men with prostate and testicular cancer. These studies are based on technologically advanced molecular methods which enable large-scale mapping of genes and molecules in a cost-effective manner in large populations. The significance of genetic and molecular differences detected will be verified in independent populations. Our hope is to identify new biomarkers for prostate cancer that can predict the clinical course, so that the patients who are in greatest need of treatment for cure are offered such. For testicular cancer, we hope to create new biological knowledge that explains why this cancer has such a strong family component. We hope that this genetic knowledge will also stimulate the development of new hypotheses regarding which environmental factors also affect the risk of testicular cancer.