Prospective investigation of polyomavirus infection and the risk of adult glioma

Kathleen M Egan,Stephanie A Smith-Warner,Tim Waterboer,Noemi Bender,Lauren R Teras,James M Hodge,Anna E Coghill,Youngchul Kim,Dana E Rollison,Tom K Grimsrud

doi:10.1038/s41598-021-89133-3

Abstract

Glioma is an aggressive primary tumor of the brain with a poorly understood etiology. We studied the association of 4 human polyomaviruses (HPyV)—JC virus (JCV), BK virus (BKV), human polyomavirus 6 (HPyV6), and Merkel cell polyomavirus (MCPyV) with glioma risk within the Cancer Prevention Study II in the US (CPS-II) and the Janus Serum Bank in Norway. Cohort participants subsequently diagnosed with glioma from the CPS-II (n = 37) and Janus Serum Bank (n = 323), a median of 6.9 and 15.4 years after blood collection, respectively, were matched to individual controls on age, sex, and date of blood draw. Serum antibodies to the major viral capsid protein (VP1) were used to establish infection history for each polyomavirus. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using conditional logistic regression. In the Janus Serum Bank, MCPyV infection was associated with a higher risk of glioma overall (OR: 1.56; 95% CI 1.10, 2.19). A modest, nonsignificant positive association with MCPyV infection was also observed in CPS-II (OR: 1.29; 95% CI 0.54, 3.08). In both cohorts, glioma risk was not significantly related to infection with JCV, BKV or HPyV6. The present study suggests that MCPyV infection may increase glioma risk.

Highlights

14.6 (5.1, 35.0) na BKV and JCV are classified as possible carcinogens[30] based on “sufficient evidence in experimental animals” but “inadequate evidence of carcinogenicity in humans”
We considered the association of glioma with seroprevalence of each of the four HPyVs, with seropositivity for each HPyV defined as virus-specific viral major capsid protein 1 (VP1) antibody level ≥ 250 MFI41
In Janus, associations of glioma with viral markers were considered overall, and according to glioma grade including WHO grade IV GBM (n = 196) and all lower glioma grades, combined (n = 127) including 56 astrocytomas (ICD-O-3: 9400-01, 9410-11, 9420, 9424-25), 27 oligodendrogliomas (9450 and 9451), 24 astrocytic tumors (9380) and 20 mixed gliomas (9382). (Data were too sparse to examine associations with individual lower grade tumors in Janus, and with nonGBMs (n = 10 cases) in Cancer Prevention Study II (CPS-II).) In the Janus Serum Bank, we examined associations according to increasing MFI as a measure of viral burden

Summary

Introduction

14.6 (5.1, 35.0) na BKV and JCV are classified as possible carcinogens[30] based on “sufficient evidence in experimental animals” but “inadequate evidence of carcinogenicity in humans”. In the only prospective study to date[31], antibodies to JCV, BKV, and simian virus 40 (SV40) measured in serum collected 1–22 years before glioma diagnosis were evaluated for association with incident glioma. Using a nested case–control design within two prospective cohort studies with biobanked collected blood, the Janus Serum Bank and the Cancer Prevention Study II (CPS-II) Nutrition cohort, we conducted an exploratory investigation of 4 polyomaviruses, JCV, BKV, HPyV6 and MCPyV, in relation to glioma risk. A multiplex assay was used to detect serum antibodies to the major capsid proteins (VP1) of each virus. To avoid potential bias in results from effects of preclinical disease on serum antibody titers, the study was restricted to cases with blood collected a minimum of 3 years (in the CPS-II) or 5 years (in the Janus Serum Bank) prior to glioma diagnosis

Methods

Results

Conclusion