Joint Effects of Epstein-Barr Virus and Polymorphisms in Interleukin-10 and Interferon-γ on Breast Cancer Risk

Background. The relationship between Epstein-Barr virus (EBV) and breast cancer (BC) is controversial. Interleukin-10 (IL-10) and interferon-gamma (IFN-gamma) are believed to play a critical role in the host's responses to EBV infection, and their genetic variations may modify the association of EBV with BC risk. Methods. We examined serum levels of EBV viral capsid antigen (VCA) immunoglobulin A (IgA) and nuclear antigen-1 (EBNA-1) IgA along with the polymorphisms of IL-10 rs1800871 and IFN-gamma rs2069705 in 354 incident BC cases and 504 age-matched controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using multivariate logistic regression. Results. VCA IgA and EBNA-1 IgA levels were positively associated with BC risk. IL-10 rs1800871 (TC/CC) was associated with a reduced BC risk (OR, 0.74 [95% CI, 0.55-1.00]) but had no interaction with EBV infection on BC risk. IFN-gamma rs2069705 was not directly associated with BC risk but interacted with EBNA-1 IgA on BC risk. Among women with the CC genotype, EBNA-1 IgA seropositivity significantly increased the risk of BC compared to EBNA-1 IgA seronegativity (OR, 5.14 [95% CI, 1.76-14.98]). Conclusions. These results suggest that EBV may contribute to the risk of BC and that this contribution may be modified by genetic variations in IFN-gamma.