Association between Epstein-Barr virus infection and risk for development of pregnancy-associated breast cancer: joint effect with vitamin D?
BACKGROUND
Few studies have evaluated the role of the ubiquitous Epstein-Barr virus (EBV) infection, together with levels of the immunomodulator, vitamin D, in different breast cancer entities. We studied, prospectively, the association of EBV and vitamin D status with the risk of pregnancy-associated breast cancer (PABC), breast cancer diagnosed during pregnancy or 1 year post-partum, using a nested case-control study.


METHODS
Serum vitamin D and antibodies to EBV were measured for 108 PABC cases of the Finnish Maternity Cohort, and 208 controls matched for date of birth, date of sampling and parity. The joint effect of vitamin D and EBV on the risk of PABC was evaluated.


RESULTS
EBV seropositivity was generally not associated with the risk of PABC. Among individuals with sufficient (≥75 nmol/l) levels of vitamin D, we, however, found similar increased risk estimates for PABC associated with serum immunoglobulin G (IgG) antibodies to EBV early antigens [odds ratio (OR)=7.7, 95% (confidence interval) CI 1.4-42.3] and the viral reactivator protein, ZEBRA (OR=7.8, 95% CI 1.1-61.2).


CONCLUSIONS
Immunological markers of EBV reactivation status among individuals with sufficient vitamin D levels were consistently associated with increased risk of the disease. This suggests that EBV reactivation may be an indicator of the progression of breast cancer occurring soon after pregnancy, while the virus probably is not the aetiological agent.
Agborsangaya
Calypse B
CB
Tampere School of Public Health, University of Tampere, Tampere, Finland. calypse.agborsangaya@uta.fi
Lehtinen
Tuula
T
Toriola
Adetunji T
AT
Pukkala
Eero
E
Surcel
Helja-Marja
HM
Tedeschi
Rosamaria
R
Lehtinen
Matti
M
D000328:Adult; D000914:Antibodies, Viral; D015415:Biomarkers / Q000378:metabolism; D001943:Breast Neoplasms / Q000097:blood / Q000821:virology*; D016022:Case-Control Studies; D020031:Epstein-Barr Virus Infections / Q000097:blood / Q000150:complications*; D005260:Female; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000097:blood / Q000821:virology*; D011252:Pregnancy Complications, Neoplastic / Q000097:blood / Q000821:virology*; D012307:Risk Factors; D015534:Trans-Activators / Q000378:metabolism; D014775:Virus Activation; D014807:Vitamin D / Q000097:blood*
D000914:Antibodies, Viral; C063676:BZLF1 protein, Herpesvirus 4, Human; D015415:Biomarkers; D007074:Immunoglobulin G; D015534:Trans-Activators; D014807:Vitamin D