Obiettivo The efficiency of DNA damage response is a subject of normal populational variations. The reduced ability to combat DNA alterations is associated with cancer susceptibility and can be attributed either to deficient DNA repair or, alternatively, to suboptimal cell death capacity. While the relationships between cancer risk and polymorphism of DNA repair genes are being intensively studied, the alternative aspect of the DNA damage response, i.e. apoptosis, has been unjustly overlooked in the research of tumour-associated gene polymorphisms.This project is aimed at testing the hypothesis whether single nucleotide polymorphisms (SNPs) associated with the reduced apoptotic capacity contribute to the increased cancer risk. The following activities will be carried out:1) Identification and validation of functional and tagging SNPs in apoptosis genes:a) Identification of already known SNPs in research publications and Internet databases;b) Validation of the occurrence of 'dubious' SNP by real-time AS-PCR genotyping;c) Search for the new SNPs in previously non-tested genes by direct DNA sequencing.2) Study on the role of apoptosis-related SNPs in cancer predisposition:a) Preliminary study of the involvement of SNP candidates in breast cancer (BC) and lung cancer (LC) susceptibility: 'comparison of extremes' approach;b) Traditionally designed, large case-control study for the promising SNP candidates. 3) Study on the functional significance of SNPs in apoptotic genes: analysis of correlation between individual genotype and the extent of apoptosis in lymphocytes exposed to DNA damaging dose of ionizing radiation.4) Comparison of the rate of DNA damage induced apoptosis in lymphocytes isolated from cancer patients vs. healthy controls.5) Comparison of radiation-induced transcriptional activation of apoptotic genes in 'high' vs. 'poor' apoptotic responders using cDNA array profiling and RT-PCR analysis.If successful, the project will significantly improve the fundamental understanding of mechanisms of cancer susceptibility as well as facilitate the development of practical approaches for the detection of at-risk individuals. Parole chiave Epidemiology Experimental & Clinical Oncology Human Genetics Programma(i) IC-INTAS - International Association for the promotion of cooperation with scientists from the independent states of the former Soviet Union (INTAS), 1993- Argomento(i) Data not available Invito a presentare proposte Data not available Meccanismo di finanziamento Data not available Coordinatore LEIDEN UNIVERSITY MEDICAL CENTER Contributo UE Nessun dato Indirizzo ALBINUSDREEF, 2 LEIDEN Paesi Bassi Mostra sulla mappa Costo totale Nessun dato Partecipanti (4) Classifica in ordine alfabetico Classifica per Contributo UE Espandi tutto Riduci tutto FINNISH INSTITUTE OF OCCUPATIONAL HEALTH (FIOH) Finlandia Contributo UE Nessun dato Indirizzo TOPELIUKSENKATU, 41 A HELSINKI Mostra sulla mappa Costo totale Nessun dato KAROLINSKA INSTITUTE Svezia Contributo UE Nessun dato Indirizzo NOBELS VÄGEN, 16 STOCKHOLM Mostra sulla mappa Costo totale Nessun dato PETROV INSTITUTE OF ONCOLOGY Russia Contributo UE Nessun dato Indirizzo LENINGRADSKAYA STR., 68 ST.PETERSBURG Mostra sulla mappa Costo totale Nessun dato THE NORWEGIAN RADIUM HOSPITAL, INSTITUTE FOR CANCER RESEARCH Norvegia Contributo UE Nessun dato Indirizzo ULLERNCHAUSSEEN, 70 OSLO Mostra sulla mappa Costo totale Nessun dato