Breast cancer risk and "delayed" primary Epstein-Barr virus infection

Parallel to its established causal association with both infectious mononuc leosis (IM) and young adulthood Hodgkin disease (YAHD), we propose a hypoth esis that "delayed" primary EBV infection (i.e., primary infection occurrin g during adolescence or adulthood) is associated with elevated breast cance r risk. We evaluated this hypothesis with two investigations, one descripti ve and the other analytic. The descriptive study used international/United States cancer registry data to assess the association between incidence rat es of breast cancer and those of YAHD, The incidence rates of the seemingly unrelated neoplasms were strongly correlated (correlation coefficients of 0.74 and 0.88 for international and United States data, respectively; these were higher than the correlation coefficients of YAHD with two other cance rs that we considered). Populations with higher incidence rates corresponde d to those with higher likelihood of delayed primary EBV infection. The ana lytical study was based on a population-based case-control study of breast cancer in middle-aged women, Age-adjusted odds ratios of breast cancer in w omen who reported a history of IM, relative to women who did not, increased monotonically from 0.55 [95% confidence interval (CI), 0.05-6.17] for wome n with 0-9 years of age at IM onset to 2.67 (CI, 1.04-6.89) for women with greater than or equal to 25 years of age at IM onset (P = 0.016), An older age at tonsillectomy, another surrogate of delayed EBV exposure, was also a ssociated with increased risk of breast cancer: odds ratios, 0.92 (CI, 0.57 -1.48) and 1.76 (CI, 1.15-2.69) for women with tonsillectomy at 0-4 years o f age and greater than or equal to 15 years of age, respectively (P = 0.018 ), Adjusting for additional potential confounders did not modify the associ ations appreciably. The implications of the findings and a potential biolog ical mechanism are presented.