An estimated 16,000-24,000 of lung cancer cases occur each year in the United States among never-smokers (15-20% of the total). Known environmental risk factors explain only a small proportion of these cases. Inflammatory conditions such as tuberculosis and chronic obstructive pulmonary disease contribute to lung carcinogenesis, and there is preliminary evidence that chronic infections with known or suspected oncogenic viruses may represent an important cause of lung cancer in never-smokers. The hypothesis of a carcinogenic role of polyoma viruses has not been tested in specifically designed epidemiologic studies. The overarching aim of this project is to investigate the association between markers of infection with polyoma viruses, and specifically JC virus and BK virus and lung cancer in never- smokers. A validated multiplex assay will be used for the serological analyses. Promising preliminary results have been obtained in the analysis of cases and controls from a retrospective case-control study. The hypothesis will be tested in serum samples of 458 never-smoking cases of lung cancer (and a comparable number of matched controls) from four on-going prospective studies, including two from Asia. The results of the serum samples will be validated arisen in series of 72 lung cancer patients who have been enrolled in a previous case-control study, from whom tumor samples will be analyzed. This study will provide novel evidence for or against a causal association between polyoma virus infection and lung cancer in never-smokers. The identification of infectious causes of cancer opens opportunities to primary prevention through vaccination and eradication.
The project is expected to generate novel results which will contribute to the understanding of the potential role of polyoma viruses (and in particular JC virus) as cause of lung cancer in never-smokers, with the ultimate goal of contributing to the prevention of this disease whose public health burden is underestimated, and understanding the mechanisms of lung carcinogenesis. If a role of polyoma viruses (as well as other oncogenic viruses) in lung cancer is demonstrated, this would open opportunities of primary prevention through the development of a vaccine, as it has been the case for HBV and HPV.