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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Exploratory/Developmental Cooperative Agreement Phase I (UH2)
Project #
1UH2CA169111-01A1
Application #
8569430
Study Section
Clinical Oncology Study Section (CONC)
Program Officer
Starks, Vaurice
Project Start
2013-09-03
Project End
2015-08-31
Budget Start
2013-09-03
Budget End
2014-08-31
Support Year
1
Fiscal Year
2013
Total Cost
$216,745
Indirect Cost
$88,872
Name
Icahn School of Medicine at Mount Sinai
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
078861598
City
New York
State
NY
Country
United States
Zip Code
10029
Malhotra, Jyoti; Waterboer, Tim; Pawlita, Michael et al. (2016) Serum biomarkers of polyomavirus infection and risk of lung cancer in never smokers. Br J Cancer 115:1131-1139