The clinical course of human infectious diseases depends on the genetic makeup of both the human host and the infecting microbe. This is especially important for chronic infections leading to cancer, because cancer is the result of a longstanding - often decades-long - interaction of a virus or a bacterium with the human host organism. Even high risk carcinogenic infectious agents will lead to cancer only in a small proportion of infected persons. Work described in this sub-project aims at identifying genetic predisposing factors of microbial carcinogens and human host that influence the risk of infection and progression towards malignancy. SP2 focusses on three infectious agents that together are responsible for more than one half of infection-associated cancers, human papilloma virus (HPV), Helicobacter pylori, and Kaposi’s sarcoma-associated herpesvirus (KSHV/HHV8). Specific objectives: Identification of polymorphic host genes that facilitate infection or the progression to infection-associated cancer Identification of bacterial genes, or variants of viral genes, associated with persistent infection and/or infection-associated cancer Development of combined microbial/host genetic markers to predict risk of malignant disease and guide preventive and treatment efforts SP2 will deliver: Microbial and host genetic markers associated with an increased risk of progression to cancer or protection against it Combinations of microbial and host markers as predictive markers that can be used in clinical decision making. Identification of novel microbial and host candidate genes functionally relevant for the induction of infection-associated cancer or MALT lymphoma. This information will be supplied to subprojects 3-5 for further functional analysis of the inflammatory signalling pathways involved and identification of potential drug targets. Development of highly sensitive methods for genetic typing of H. pylori in archived tissues, which will be enabling to other sub-projects and the scientific community.