Abstract 4290: Serum biomarkers of polyomavirus infection and risk of lung cancer in never smokers
Authors: Malhotra Jyoti , Waterboer Tim , Pawlita Michael , Michel Angelika , Cai Qiuyin , Zheng Wei , Lan Qing , Rothman Nathaniel , Langseth Hilde , Grimsrud Tom K. , Yuan Jian-Min , Koh Woon-Puay , Arslan Alan A. , Zeleniuch-Jacquotte Anne , Boffetta Paolo 
Published: July 2016

Abstract
Background: Lung cancer in never smokers is a significant contributor of cancer mortality. As the incidence of lung cancer in never smokers is increasing, there is a need to investigate risk factors for lung cancer in this population. There is data to support that polyomaviruses are potentially carcinogenic in the human lung. We explored the role of polyomaviruses in lung cancer development in never smokers using a multiplex assay to detect serum antibodies to viral capsid proteins.
Methods: We conducted a nested case-control study of never-smoking cases of lung cancer identified from four established prospective cohorts- NYU Women's Health Study (NYU-WHS), Janus Serum Bank, Shanghai Women's Health Study (SWHS) and Singapore Chinese Health Study (SCHS). Controls were matched to cases on gender, never-smoking status, age and calendar period of entry. Serological analysis was performed using a 100 μL pre-diagnostic serum sample at the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) in Heidelberg, Germany using fluorescent bead-based multiplex serology and included antibodies to viral capsid protein-1 and T-antigens of 9 human polyomaviruses: JC virus, BK virus, KI virus, WU virus, Trichodysplasia Spinulosa-associated Polyoma Virus, Merkel Cell Polyoma Virus, Human Polyoma Virus 6, Human Polyoma Virus 7 and Human Polyoma Virus 10.
Results: The final analysis included 511 cases and 508 controls. Mean age of participants was 56.1±11.0 years. SWHS and SCHS included only Asian participants. NYU-WHS and SWHS had only female participants. Nearly 85% of the participants in our pooled analysis were females and 74% were Asians. Seropositivity for each polyomavirus showed significant heterogeneity by study but overall there were no statistical significant differences between cases and controls for any of the polyomaviruses. 72.0% of the cases and 71.5% of the controls were seropositive for JC virus antibody. Seropositivity for BK virus was higher at 89.0% in cases and 89.8% in controls. We did not find any difference in seropositivity between cases and controls in our stratified analysis based on gender, histology or time interval from sample collection to cancer diagnosis. We also performed sensitivity analyses and found the seroprevalence data to be very robust to alterations in the MFI cutpoints.
Conclusions: Our study is the largest epidemiological study in never smokers to investigate the role of polyomaviruses in lung cancer development. We did not find a significant difference in serological measurements of antibodies against each of the polyomaviruses between the cases and controls. Future research to evaluate the relationship between polyomaviruses and lung carcinogenesis should focus on evaluating viral replication in tumor in combination with serological markers of infection especially as antibody reactivities can vary considerably across different populations and geographical areas as demonstrated by our study.
Citation Format: Jyoti Malhotra, Tim Waterboer, Michael Pawlita, Angelika Michel, Qiuyin Cai, Wei Zheng, Qing Lan, Nathaniel Rothman, Hilde Langseth, Tom K. Grimsrud, Jian-Min Yuan, Woon-Puay Koh, Alan A. Arslan, Anne Zeleniuch-Jacquotte, Paolo Boffetta. Serum biomarkers of polyomavirus infection and risk of lung cancer in never smokers. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4290.