Dr. Vessela Kristensen from the Norwegian Radium Hospital will discuss the effect of single nucleotide polymorphism (SNP) in selected genes from the reactive oxygen species (ROS) biochemical and signalling pathways on genome-wide expression in tumours from breast cancer patients.
 Vessela N. Kristensen |
Place: Agricultural University of Norway, Soil Science building (Jordfagbygningen/Saghellinga), room J106. Building no. 35 on the map
Speaker: Dr. Vessela N. Kristensen, Dept. of Genetics, Norwegian Radium Hospital
Abstract
The genes were selected from around 4000 MEDLINE entries and different databases (OMIM, HUGO) to create the genotype profile of all genes involved in the regulation of the redox level in the cells, ROS mediated signalling and repair of DNA-damages caused by ROS. These pathways are of crucial importance for the gene-environmental interactions leading to cancer initiation, as well as in the state of hypoxia during cancer progression. In addition both radiation and a large number of chemotherapies exert their antineoplastic effect by either directly attacking cellular macromolecules, including DNA or indirectly, by generating ROS and subsequent by-products. Genome-wide expression analyses have previously been performed on tumour biopsies taken prior to the treatment and at final surgery. To identify the cis- and trans- regulatory SNPs within a given pathway we merged our SNP and mRNA expression databases. 718 SNPs in the pathway-selected genes were studied using blood DNA from breast cancer patients with locally advanced disease; genome-wide gene expression analyses have previously been performed. In a parallel study the interactions between genetic polymorphism (SNPs) in the estradiol pathway and hormone levels in the plasma of 109 healthy post-menopausal women are reported. Again two types of data were used in the analysis: categorical measurements of 18 SNP's; and quantitative measurements of plasma levels of steroids. Several SNPs were found with significantly different distribution in the below and above median levels of estrone (E1) and estradiol (E2). To analyse the data we either divided the patients into classes according to their genotypes, and searched for differences in the quantitative trait (m RNA or metabolic expression levels), or we grouped the patients according to mRNA or metabolic expression levels and searched for the distribution of genotypes in each group. The methods involved in these studies will be discussed.
Research interests
Dr. Vessela N. Kristensen has been at the Department of Genetics, DNR since March 1996. During her first two postdoctoral years (96-97), the pilot studies for genetic susceptibility to breast cancer in relation to hormonal metabolism were performed and she could show the viability and the perspective of SNP studies at DNR. She pioneered the work with the genetic polymorphisms of CYP19 (aromatase), and a series of studies including a recent study in the Journal of the National Cancer Institute (2004, Vol 96, No 12, p 936) confirmed these pilot results. This work led to a post-doctoral fellowship from the Norwegian Cancer Society (1999-2002), GENETIC VARIATION, CANCER RISK AND MODULATION OF THERAPY RESPONSE IN BREAST CANCER, which enabled the further development of the project from SNP and susceptibility to drug response. She is presently at a research position at the same Department. She spent 2003 in the laboratory for high throughput cancer genomics at the Advanced Technology Center, NCI, NIH, where she is a visiting scientist still.
The field of genetic polymorphisms is an essential part not only of the susceptibility and prevention problematics, not only of the populational aspects of the cancer disease, but also because genetic polymorphism may affect each molecular interaction in the cancer progression and treatment. Starting with a few SNPs in 1996, the lab is now currently able to genotype thousands and to see patterns in a much more detailed picture as well as to elucidate the functional significance of many of the SNPs.
For a description of ongoing projects please see this link
