Abstract
Epstein-Barr virus (EBV) has been implicated in several human cancers, but its broader cancer risk remains unclear. We investigated the association between EBV VCA-IgA antibody levels and cancer risk in two large prospective cohorts from Southern China, comprising 73,939 adults. During around 8-10 years follow-up, 964 and 1026 incident cancer cases were identified in the Zhongshan and Wuzhou cohorts. VCA-IgA seropositivity was associated with higher age-standardized incidence rates for total cancer significantly. In pooled analyses, VCA-IgA seropositive individuals had higher risks of total cancer (HR 4.88, 95% CI: 2.84-8.37), lung cancer (1.76, 1.23-2.54), liver cancer (1.70, 1.10-2.63), nasopharyngeal carcinoma (26.05, 11.77-57.65), and lymphoma (3.20, 1.46-6.99) compared to seronegative individuals. The associations showed an increased dose-response pattern, and keep persistent even up to ten years prior to diagnosis. The population-attributable risk percentage for total cancer due to VCA-IgA seropositivity is estimated at 7.8%. These findings provide prospective evidence that EBV seropositivity is associated with increased risks of multiple cancers. This association results in a heightened attributed cancer burden in Southern China.