Objective
The central idea of the project is to examine the advantages of the non-traditional approach for the studies of gene-disease interactions. Whereas investigations of gene polymorphism usually rely on the age- and behaviour-matched numerous case-control groups, the proposers suggest facilitating the analysis by the comparison of extremities. For instance, the impact of selected genetic polymorphisms (CYP1A1, CYP2D6, CYP2E1, GSTM1, GSTM3, NAT1, NAT2, and L-MYC) will be evaluated on the lung cancer model, by focusing on the allele picture in elderly tumour-free heavy smokers (150 subjects) vs. either affected non-smokers (150 patients) or young light smokers with pulmonary neoplasia (150 patients). Such a concentration on "cancer-resistant" vs. "cancer-prone" cohorts is expected to maximize the differences in allele distribution if the locus of interest indeed contributes in the disease risk. To be able to check the validity of the conclusions, traditional case-control study (250 middle-aged healthy donors vs. 200 "usual" lung cancer cases) will also be performed.
Technically, the project consists of
1) recruiting of subjects and DNA isolation;
2) DNA genotyping;
3) the data analysis.
First step will be achieved by NIS partners; Russian geneticists will transfer the DNA collection technology to the clinical team from Moldova.
Second step will be done by collaboration of EC and Russian partners; this will include establishment of some novel techniques in Russian laboratory under the guidance of EC teams; then genotyping obligations will be shared among the Russian, UK, German and Finnish partners.
Data analysis will be performed by joint efforts of all participants: Moldovian team will provide clinical expertise; Russian team will organize the whole body of the data; Finnish and UK team will perform the statistical analysis; writing of manuscripts will be shared according to genotyping obligations under the guidance of the Co-ordinator of the project and the Partner-Consultant.
The main expected output of the project is a contribution in the methodology of polymorphism research. An inclusion of "lung cancer resistant" group of elderly tumour-free heavy smokers in the investigation is believed to emphasize the discrepancies between prone and tolerant genotypes. In the case of positive outcome this approach could provide a tool for express-screening programmes. Noteworthy, the proposers have already reported preliminary data, which support the viability of the suggested design.
Other results are:
1) Specification of the role of genetic polymorphism of CYP1A1, CYP2D6, CYP2E1, GSTM1, GSTM3, NAT1, NAT2, and L-MYC genes in the lung cancer predisposition; evaluation of the impact of the gene-gene interactions;
2) Estimation of the interethnic differences in the allele distribution of mentioned loci among Caucasians;
3) Transfer of the laboratory techniques and the "style" of polymorphism research from the Russian co-participant to Moldovian one, and from EC partners to the Russian group.
Topic(s)
Call for proposal
Data not availableFunding Scheme
Data not availableCoordinator
00250 Helsinki
Finland